WO2021067644A1

WO2021067644A1 - Combination therapy with immune stimulatory conjugates

Info

Publication number: WO2021067644A1
Application number: PCT/US2020/053870
Authority: WO
Inventors: Valerie Odegard; Peter R. Baum; Peter A. Thompson
Original assignee: Silverback Therapeutics, Inc.
Priority date: 2019-10-01
Filing date: 2020-10-01
Publication date: 2021-04-08
Also published as: AU2020358726A1; CA3151322A1

Abstract

Combination therapies using a conjugate comprising a TLR agonist and an antibody that binds a tumor associated antigen or liver cell antigen, and a second therapeutic agent, such as an immune checkpoint inhibitor, are provided for treating cancer or viral infections. Combination therapies using a conjugate comprising a TLR agonist and an antibody that binds HER2, and a second therapeutic agent are also provided for treating cancer.

Description

COMBINATION THERAPY WITH IMMUNE STIMULATORY CONJUGATES STATEMENT REGARDING SEQUENCE LISTING The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is 860234_412WO_SEQUENCE_LISTING.txt. The text file is 9 KB, was created on September 17, 2020, and is being submitted electronically via EFS-Web. BACKGROUND Technical Field [0001] The present application relates to combination therapies comprising immune-stimulatory conjugates and methods for treating cancer or viral infections. Description of the Related Art [0002] One of the leading causes of death in the United States is cancer. Conventional methods of cancer treatment, like chemotherapy, surgery, or radiation therapy, tend to be highly toxic and/or nonspecific to a cancer, resulting in limited efficacy and harmful side effects. The immune system has the potential to be a powerful, specific tool in fighting cancers. This observation has led to the development of immunotherapeutics as drug candidates for clinical trials. Immunotherapeutics can act by boosting a specific immune response and have the potential to be a powerful anti-cancer treatment. Such immunotherapeutics may comprise benzazepine compounds, which in some instances, act as toll-like receptor (e.g., TLR8) agonists. INCORPORATION BY REFERENCE [0003] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF SUMMARY [0004] The present disclosure provides tumor-associated antigen- or liver cell antigen-dependent uptake of a Toll-like receptor (TLR) agonist, which allows for systemic delivery of an innate immune agonist that generates tumor- or liver-localized immune cell activation while avoiding systemic toxicity. In some embodiments, a method of treating cancer or viral infection is provided, comprising administering to a subject with cancer or viral infection a conjugate comprising a TLR agonist and an antibody that binds a tumor-associated or liver cell antigen, and an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor inhibits PD-1 and/or PD-L1. In some embodiments, the TLR agonist is a TLR8 agonist. [0005] In certain embodiments, a method of treating cancer or viral infection is provided, comprising administering to a subject with cancer or viral infection a conjugate and an immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1; wherein the conjugate is represented by Formula (I):

wherein: A is an antibody that binds a tumor associated antigen or a liver cell antigen, L is a linker; D_x is a TLR8 agonist, wherein the TLR8 agonist is a benzazepine compound; n is selected from 1 to 20; and z is selected from 1 to 20. [0006] In further embodiments, a method of treating a HER2-expressing cancer is provided, comprising administering to a subject with a HER2-expressing cancer a conjugate and an additional therapeutic agent comprising a HER2-targeted agent such as a kinase inhibitor, a therapeutic agent comprising an anti-HER2 antibody, or both; wherein the conjugate is represented by Formula (I):

wherein: A is an antibody that binds HER2, L is a linker; D_x is a TLR8 agonist, wherein the TLR8 agonist is a benzazepine compound; n is selected from 1 to 20; and z is selected from 1 to 20. BRIEF DESCRIPTION OF THE DRAWINGS [0007] Certain features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative aspects, in which the principles of the disclosure are utilized, and the accompanying drawings of which: [0008] FIGS.1A-1B show increased expression levels of CD86 (FIG.1A) and PD-L1 (FIG.1B) in dendritic cells following exposure to HER2-TLR8 in the presence of HER2-expressing tumor cells, as described in Example 1. [0009] FIG.2 shows IFN-γ expression in human PBMCs co-cultured with SK- BR-3 (3+ HER2+ tumor cell line), MDA-MB-453 (2+ HER2+ tumor cell line), or MDA-MB-468 (HER2- tumor cell line) in the presence of HER2-TLR8 for 24 hours, as described in Example 2. [0010] FIG.3 shows the similarity in expression between TLR7 in mouse and TLR8 in human dendritic cells and macrophages, as described in Example 3. [0011] FIGS.4A-4K show single agent efficacy of a HER2-TLR7 (mouse surrogate for human HER2-TLR8) in an in vivo xenograft mouse model, as described in Example 4. The arrows indicate the day a dose was administered to the mice. Slopes of growth curves contrasting unconjugated HER2 mAb against HER2-TLR7 are significantly different (p < 0.001) at each dose level. [0012] FIGS.5A-5B show the upregulation of PD-L1 on the surface of HER2- expressing tumor cells following treatment with the HER2-TLR8 surrogate, HER2- TLR7, 48 hours after: (FIG.5A) a single dose or (FIG.5B) the third of three doses, as described in Example 5. [0013] FIGS.6A-6C show (FIG.6A) IP10 expression and IFN-γ expression at day 2 (FIG.6B) and day 7 (FIG.6C) in EMT6 tumors from mice treated once with HER2-TLR7 mouse surrogate at 10mg/kg, unconjugated anti-HER2 antibody at 10mg/kg, isotype control antibody at 10mg/kg, each alone or in combination with anti PD-1 antibody, as described in Example 6. [0014] FIGS.7A-7F show spider plots of the anti-tumor response in mice with HER2+ tumors after treatment with (FIG.7F) HER2-TLR7 in combination with an anti-PD1 antibody, as compared to treatment with (FIG.7A) combinations of isotype control antibodies (rlgG2a and mIgG2a, (FIG.7B) mIgG2a/HER2 mAb, (FIG.7C) mIgG2a/HER2-TLR7, (FIG.7D) anti-PD1/mIgG2a, or (FIG.7E) anti-PD1/HER2 mAb, as described in Example 7. [0015] FIGS.8A-8B show the interactions of HER2-TLR8 and hz4D5 with monomeric human HER2 ECD were evaluated using Octet Red 96TM in 2 orientations FIG.8A shows monomeric human HER2 ECD with 10x histidine tag immobilized to penta-his sensor used to capture HER2-TLR8 until saturation and then tested for additive binding against itself, HER2-TLR8 (solid line), or hz4D5 (broken line). Increased signal of hz4D5 is observed after HER2-TLR8 has saturated HER2 ECD indicates HER2-TLR8 and hz4D5 occupy different epitopes on HER2 ECD. FIG.8B is the same assay set-up as in FIG.8A, except with hz4D5 captured until saturation and then tested for additive binding against itself, hz4D5 (broken line), or HER2-TLR8 (solid line). Increased signal of HER2-TLR8 is observed after hz4D5 has saturated HER2 ECD additionally indicates HER2-TLR8 and hz4D5 occupy different epitopes on HER2 ECD. [0016] FIG.9 shows that the HER2-TLR8 agonist conjugate does not impede the function of the trastuzumab-like antibody, hz4D5, of reducing tumor cell viability in vitro, as described in Example 9. [0017] FIGS.10A-10F. FIGS.10A-10D show TNF-α production in co- cultures of various HER2+ (FIGS.10A-10C) or HER2- (FIG.10D) tumor cell lines and PBMCs contacted with HER2-TLR8, unconjugated trastuzumab-like anti-HER2 antibody, and a combination of both, as described in Example 10. FIGS.10E-10F show IFN-γ expression in co-cultures of a HER2+ (FIG.10E) or HER2- (FIG.10F) tumor cell line and PBMCs contacted with HER2-TLR8, unconjugated trastuzumab-like anti- HER2 antibody, and a combination of both, as described in Example 10. [0018] FIGS.11A-11F show spider plots of an anti-tumor response in SCID mice with HER2+ NCI N87 tumors following treatment with 10 mg/kg HER2-TLR7, matched unconjugated HER2 mAb, or isotype control antibody, alone or in combination with the trastuzumab-like antibody, hz4D5. The arrows indicate dose administration. [0019] FIGS.12A-12F show that HER2-TLR7 surrogate in combination with trastuzumab-like monoclonal antibody, hz4D5, results in enhanced efficacy over the single agents alone, as described in Example 12. Arrows indicate day dose was administered. DETAILED DESCRIPTION [0020] Immune checkpoint inhibition therapy has been largely ineffective as single agent therapies in tumors, in part due to the absence of a T cell infiltrate. An abundant myeloid cell population within checkpoint refractory tumors provides an attractive target with the potential to expand and recruit tumor-specific cytotoxic T lymphocytes (CTLs). Single agent therapies for chronic viral infections, such as Hepatitis B virus (HBV) and Hepatitis C virus (HCV), have been equally ineffective. The present disclosure demonstrates for the first time that in vivo treatment with a TLR8 agonist, when conjugated to an antibody, drives anti-tumor or anti-viral immunity, which in turn results in PD-L1 upregulation, a negative regulator of T cell activation. This PD-L1 induction is expected to be in the tumor microenvironment or in infected liver. The combination of immune checkpoint inhibitor and TLR8 agonist antibody conjugate results in a more profound T cell response as demonstrated by enhanced IFN-γ production and ultimately enhanced efficacy compared to either agent alone. In addition, in the context of an immune competent tumor-bearing mouse, a TLR7 agonist (used as a TLR8 agonist surrogate) conjugated to an anti-HER2 antibody caused an expansion in intra-tumoral, neo-antigen specific CD8+ T cells and robust myeloid cell activation. In the case of HER2+ disease and given the current standard of care for patients with HER2+ disease often includes HER2-directed agents that show clinical benefit, the ability of a TLR8 agonist conjugated to an anti-HER2 antibody to combine with HER2 directed agents to further lower tumor burden, as provided in the present disclosure, is expected to be clinically useful. [0021] Additional aspects and advantages of the present disclosure will become apparent to those skilled in this art from the following detailed description, wherein illustrative aspects of the present disclosure are shown and described. As will be appreciated, the present disclosure is capable of other and different aspects, and its several details are capable of modifications in various respects, all without departing from the disclosure. Accordingly, the descriptions are to be regarded as illustrative in nature, and not as restrictive. [0022] As used herein, a “tumor associated antigen” or “tumor antigen” refers to an antigen present on a cancer cell that can be recognized by an antibody and is preferentially present on a cancer cell as compared to normal (non-cancerous) cells. [0023] As used herein, the term “antibody” refers to an immunoglobulin molecule that specifically binds to, or is immunologically reactive toward, a specific antigen. The portion of the antibody that binds a specific antigen may be referred to as an “antigen binding domain.” The term antibody can include, for example, polyclonal, monoclonal, genetically engineered, and antigen binding fragments thereof. An antibody can be, for example, murine, chimeric, humanized, a heteroconjugate, bispecific, diabody, triabody, or tetrabody. An antigen binding fragment can include, for example, a Fab ^, F(ab ^)₂, Fab, Fv, rIgG, scFv, hcAbs (heavy chain antibodies), a single domain antibody, V_HH, V_NAR, sdAbs, or nanobody. [0024] As used herein, “recognize” refers to the specific association or specific binding between an antigen binding domain and an antigen. Specific association or specific binding does not require that the antigen binding domain does not associate with or bind to any other antigen, but rather that it preferentially associates with or binds to the antigen, as compared to association with or binding to an unrelated antigen. [0025] As used herein, “specifically binds” and the like refers to the specific association or specific binding between the antigen binding domain and the antigen, as compared with the interaction of the antigen binding domain with a different antigen (i.e., non-specific binding). In some embodiments, an antigen binding domain that recognizes or specifically binds to an antigen has a dissociation constant (K_D) of <100 nM, <10 nM, <1 nM, <0.1 nM, <0.01 nM, or <0.001 nM (e.g.10^-8 M or less, e.g. from 10^-8 M to 10^-13 M, e.g., from 10^-9 M to 10^-13 M). Specific binding does not require that the antigen binding domain does not associate with or bind to any other antigen, but rather that it preferentially associates with or binds to the antigen, as compared to association with or binding to an unrelated antigen. [0026] As used herein, an “Fc domain” refers to a domain from an Fc portion of an antibody that can specifically bind to an Fc receptor, such as a Fcgamma receptor or an FcRn receptor. [0027] As used herein, a “myeloid cell” refers to a dendritic cell, a macrophage, a monocyte, a myeloid derived suppressor cell (MDSC). [0028] As used herein, an “antigen presenting cell” or “APC” refers to a cell that can present antigen to a T-, or B-cell, in a productive manner leading to activation and/or expansion of T-, or B-cell clones specific for said antigen. Nonlimiting exemplary APCs include dendritic cells, macrophages, monocytes, and B cells. In some embodiments, an antigen presenting cell is a dendritic cell, a macrophage, or a monocyte. [0029] As used herein, an “immune stimulatory compound” is a compound that activates or stimulates an immune cell, such as a myeloid cell or an APC. [0030] As used herein, a “myeloid cell agonist” refers to a compound that activates or stimulates an immune response by a myeloid cell. [0031] As used herein, a “benzazepine compound” refers to small molecule chemical compound comprising a benzazepine moiety, where the benzazepine moiety is a benzene ring fused to a 7-membered ring that comprises one or two nitrogen ring members. In addition to the bond where the ring is fused to the benzene ring, the 7- membered ring includes two double bonds (e.g., an azepine or diazepine ring), one double bond (e.g., a dihydroazepine or dihydro-diazepine ring), or no double bonds (e.g., a tetrahydroazepine, azepane, tetrahydrodiazepine, or diazepane ring). The benzazepine moiety is optionally substituted. In some embodiments, the benzazepine moiety is an optionally substituted 4,5-dihydro-3H-benzo[b]azepine. In some embodiments, the benzazepine moiety has the structure:

wherein is a double bond or a single bond; L² is selected from –X²-, -X²-C_1-6 alkylene-X²-, -X²-C_2-6 alkenylene-X²-, and – X²-C_2-6 alkynylene-X²-, each of which is optionally substituted on alkylene, alkenylene or alkynylene with one or more R¹²; X² at each occurrence is independently selected from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, -C(O)N(R¹⁰)C(O)N(R¹⁰), -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-, -S(O)₂-, -OS(O)-, -S(O)O-, -S(O), -OS(O)₂-, -S(O)₂O, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and –N(R¹⁰)S(O)N(R¹⁰)-; R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and –CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C_3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl; R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and –S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; and R¹⁰ is independently selected at each occurrence from hydrogen, -NH2, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; and the moiety is optionally substituted at any position. [0032] A “small molecule” is an organic compound with a molecular weight of less than 1500, or 100, or 900, or 750, or 600, or 500 Daltons. In some embodiments, a small molecule agonist has an octanol-water partition coefficient (logP) in the range of from 3 to 6, or from 4 to 5, or from 2 to 4. In some embodiments, a small molecule agonist has a polar surface area of less than 200, or less than 150 Å². In some embodiments, the small molecule agonist has not more than five, or not more than three, hydrogen bond donors, and not more than 10, or not more than three hydrogen bond acceptors. A small molecule myeloid cell agonist is not a protein, a polysaccharide, or a nucleic acid. In some embodiments, a small molecule is an immune checkpoint inhibitor, such as a PD-1 or PD-L1 inhibitor, or a HER2 inhibitor. [0033] As used herein, the term “conjugate” refers to a polypeptide attached to at least one compound, optionally via a linker(s). In some embodiments, the polypeptide is an antibody or antigen binding fragment thereof. [0034] As used herein, an “immune-stimulatory conjugate” refers to a conjugate that activates or stimulates the immune system or a portion thereof, as determined by an in vitro or in vivo assay. [0035] As used herein, an “immune cell” refers to a T cell, B cell, NK cell, NKT cell, or an antigen presenting cell. In some embodiments, an immune cell is a T cell, B cell, NK cell, or NKT cell. In some embodiments, an immune cell is an antigen presenting cell. In some embodiments, an immune cell is not an antigen presenting cell. [0036] The terms “salt” or “pharmaceutically acceptable salt” refer to salts derived from a variety of organic and inorganic counter ions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharmaceutically acceptable base addition salt is chosen from ammonium, potassium, sodium, calcium, and magnesium salts. [0037] The term “Cx-y” when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain. For example, the term “C_1-6 alkyl” refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups that contain from 1 to 6 carbons. The term –C_x-y alkylene- refers to a substituted or unsubstituted alkylene chain with from x to y carbons in the alkylene chain. For example –C_1-6 alkylene- may be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted. [0038] The terms “C_x-y alkenyl” and “C_x-y alkynyl” refer to substituted or unsubstituted unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively. The term –Cx-y alkenylene- refers to a substituted or unsubstituted alkenylene chain with from x to y carbons in the alkenylene chain. For example, –C_2-6 alkenylene- may be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. An alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. The term –C_x-y alkynylene- refers to a substituted or unsubstituted alkynylene chain with from x to y carbons in the alkenylene chain. For example, – C_2-6 alkenylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. An alkynylene chain may have one triple bond or more than one triple bond in the alkynylene chain. [0039] “Alkylene” refers to a divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and preferably having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through the terminal carbons respectively. In other embodiments, an alkylene comprises one to five carbon atoms (i.e., C₁-C₅ alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (i.e., C₁-C₄ alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (i.e., C₁-C₃ alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (i.e., C₁-C₂ alkylene). In other embodiments, an alkylene comprises one carbon atom (i.e., C₁ alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (i.e., C5-C8 alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (i.e., C₂-C₅ alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (i.e., C₃-C₅ alkylene). Unless stated otherwise specifically in the specification, an alkylene chain is optionally substituted by one or more substituents such as those substituents described herein. [0040] “Alkenylene” refers to a divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group are through the terminal carbons respectively. In other embodiments, an alkenylene comprises two to five carbon atoms (i.e., C₂-C₅ alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (i.e., C₂-C₄ alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (i.e., C₂-C₃ alkenylene). In other embodiments, an alkenylene comprises two carbon atoms (i.e., C₂ alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (i.e., C₅-C₈ alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (i.e., C3-C5 alkenylene). Unless stated otherwise specifically in the specification, an alkenylene chain is optionally substituted by one or more substituents such as those substituents described herein. [0041] “Alkynylene” refers to a divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group are through the terminal carbons respectively. In other embodiments, an alkynylene comprises two to five carbon atoms (i.e., C₂-C₅ alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (i.e., C₂-C₄ alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (i.e., C₂-C₃ alkynylene). In other embodiments, an alkynylene comprises two carbon atoms (i.e., C2 alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (i.e., C₅-C₈ alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (i.e., C₃-C₅ alkynylene). Unless stated otherwise specifically in the specification, an alkynylene chain is optionally substituted by one or more substituents such as those substituents described herein. [0042] “Heteroalkylene” refers to a divalent hydrocarbon chain including at least one heteroatom in the chain, containing no unsaturation, and preferably having from one to twelve carbon atoms and from one to 6 heteroatoms, e.g., -O-, -NH-, -S-. The heteroalkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the heteroalkylene chain to the rest of the molecule and to the radical group are through the terminal atoms of the chain. In other embodiments, a heteroalkylene comprises one to five carbon atoms and from one to three heteroatoms. In other embodiments, a heteroalkylene comprises one to four carbon atoms and from one to three heteroatoms. In other embodiments, a heteroalkylene comprises one to three carbon atoms and from one to two heteroatoms. In other embodiments, a heteroalkylene comprises one to two carbon atoms and from one to two heteroatoms. In other embodiments, a heteroalkylene comprises one carbon atom and from one to two heteroatoms. In other embodiments, a heteroalkylene comprises five to eight carbon atoms and from one to four heteroatoms. In other embodiments, a heteroalkylene comprises two to five carbon atoms and from one to three heteroatoms. In other embodiments, a heteroalkylene comprises three to five carbon atoms and from one to three heteroatoms. Unless stated otherwise specifically in the specification, a heteroalkylene chain is optionally substituted by one or more substituents such as those substituents described herein. [0043] The term “carbocycle” as used herein refers to a saturated, unsaturated or aromatic ring in which each atom of the ring is carbon. Carbocycle includes 3- to 10- membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. In an exemplary embodiment, an aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. A bicyclic carbocycle includes any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits. A bicyclic carbocycle includes any combination of ring sizes such as 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. The term “unsaturated carbocycle” refers to carbocycles with at least one degree of unsaturation and excluding aromatic carbocycles. Examples of unsaturated carbocycles include cyclohexadiene, cyclohexene, and cyclopentene. [0044] The term “heterocycle” as used herein refers to a saturated, unsaturated or aromatic ring comprising one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings, 6- to 12-membered bicyclic rings, and 6- to 12-membered bridged rings. A bicyclic heterocycle includes any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits. In an exemplary embodiment, an aromatic ring, e.g., pyridyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, morpholine, piperidine or cyclohexene. A bicyclic heterocycle includes any combination of ring sizes such as 4-5 fused ring systems, 5-5 fused ring systems, 5- 6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. The term “unsaturated heterocycle” refers to heterocycles with at least one degree of unsaturation and excluding aromatic heterocycles. Examples of unsaturated heterocycles include dihydropyrrole, dihydrofuran, oxazoline, pyrazoline, and dihydropyridine. [0045] The term “heteroaryl” includes aromatic single ring structures, preferably 5- to 7-membered rings, more preferably 5- to 6-membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. The term “heteroaryl” also includes polycyclic ring systems having two or more rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is heteroaromatic, e.g., the other rings can be aromatic or non-aromatic carbocyclic, or heterocyclic. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like. [0046] The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons or substitutable heteroatoms, e.g., -NH-, of the structure. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon with an oxo, imino or thioxo group. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. [0047] In some embodiments, substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO₂), imino (=N-H), oximo (=N-OH), hydrazino (=N-NH2), -R^b-OR^a, -R^b- OC(O)-R^a, -R^b-OC(O)-OR^a, -R^b-OC(O)-N(R^a)₂, -R^b-N(R^a)₂, -R^b-C(O)R^a, -R^b- C(O)OR^a, -R^b-C(O)N(R^a)₂, -R^b-O-R^c-C(O)N(R^a)₂, -R^b-N(R^a)C(O)OR^a, -R^b- N(R^a)C(O)R^a, -R^b-N(R^a)S(O)_tR^a (where t is 1 or 2), -R^b-S(O)_tR^a (where t is 1 or 2), -R^b- S(O)tOR^a (where t is 1 or 2), and -R^b-S(O)tN(R^a)₂ (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO₂), imino (=N- H), oximo (=N-OH), hydrazine (=N-NH₂), -R^b-OR^a, -R^b-OC(O)-R^a, -R^b-OC(O)-OR^a, -R^b-OC(O)-N(R^a)₂, -R^b-N(R^a)₂, -R^b-C(O)R^a, -R^b-C(O)OR^a, -R^b-C(O)N(R^a)₂, -R^b-O-R^c- C(O)N(R^a)₂, -R^b-N(R^a)C(O)OR^a, -R^b-N(R^a)C(O)R^a, -R^b-N(R^a)S(O)tR^a (where t is 1 or 2), -R^b-S(O)_tR^a (where t is 1 or 2), -R^b-S(O)_tOR^a (where t is 1 or 2) and -R^b-S(O)_tN(R^a)₂ (where t is 1 or 2); wherein each R^a is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each R^a, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO₂), imino (=N-H), oximo (=N-OH), hydrazine (=N-NH₂), -R^b-OR^a, -R^b-OC(O)-R^a, -R^b-OC(O)-OR^a, -R^b-OC(O)-N(R^a)₂, -R^b-N(R^a)₂, -R^b-C(O)R^a, -R^b-C(O)OR^a, -R^b-C(O)N(R^a)₂, -R^b-O-R^c-C(O)N(R^a)₂, -R^b- N(R^a)C(O)OR^a, -R^b-N(R^a)C(O)R^a, -R^b-N(R^a)S(O)_tR^a (where t is 1 or 2), -R^b-S(O)_tR^a (where t is 1 or 2), -R^b-S(O)tOR^a (where t is 1 or 2) and -R^b-S(O)tN(R^a)₂ (where t is 1 or 2); and wherein each R^b is independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each R^c is a straight or branched alkylene, alkenylene or alkynylene chain. [0048] It will be understood by those skilled in the art that substituents can themselves be substituted, if appropriate. Unless specifically stated as “unsubstituted,” references to chemical moieties herein are understood to include substituted variants. For example, reference to a “heteroaryl” group or moiety implicitly includes both substituted and unsubstituted variants. [0049] In addition, it should be understood that the individual compounds (e.g., proteins), or groups of compounds, derived from the various combinations of the structures and substituents (e.g., domains, regions or peptide components) described herein, are disclosed by the present application to the same extent as if each compound or group of compounds was set forth individually. Thus, selection of particular structures or particular substituents is within the scope of the present disclosure. [0050] Chemical entities having carbon-carbon double bonds or carbon-nitrogen double bonds may exist in Z- or E- form (or cis- or trans- form). Furthermore, some chemical entities may exist in various tautomeric forms. Unless otherwise specified, chemical entities described herein are intended to include all Z-, E- and tautomeric forms as well. [0051] A “tautomer” refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. The compounds presented herein, in certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibrium include:

. [0052] The phrases “intravenous administration” and “administered intravenously” as used herein refer to injection or infusion of a conjugate into a vein of a subject. [0053] The phrases “intravenous slow infusion” and “IV slow infusion” as used here refer to an intravenous infusion that results in a Tmax of about 4 hours or more. [0054] The phrases “subcutaneous administration,” “subcutaneously administering” and the like refer to administration of a conjugate into the subcutis of a subject. For clarity, a subcutaneous administration is distinct from an intratumoral injection into a tumor or cancerous lesion located in the subcuta. [0055] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. [0056] As used herein, “identical” or “identity” refer to the similarity between a DNA, RNA, nucleotide, amino acid, or protein sequence to another DNA, RNA, nucleotide, amino acid, or protein sequence. Identity can be expressed in terms of a percentage of sequence identity of a first sequence to a second sequence. Percent (%) sequence identity with respect to a reference DNA sequence can be the percentage of DNA nucleotides in a candidate sequence that are identical with the DNA nucleotides in the reference DNA sequence after aligning the sequences. “Percent (%) sequence identity with respect to a reference amino acid sequence can be the the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. The percentage sequence identity values can be generated using the NCBI BLAST 2.0 software as defined by Altschul et al. (1997) “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs,” Nucleic Acids Res.25:3389-3402, with the parameters set to default values. [0057] The term “about” as used herein in the context of a number refers to a range centered on that number and spanning 10% less than that number and 10% more than that number. The term “about” used in the context of a range refers to an extended range spanning 10% less than that the lowest number listed in the range and 10% more than the greatest number listed in the range. [0058] In the present description, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated. Also, any number range recited herein relating to any physical feature, such as polymer subunits, size or thickness, are to be understood to include any integer within the recited range, unless otherwise indicated. It should be understood that the terms “a” and “an” as used herein refer to “one or more” of the enumerated components. The use of the alternative (e.g., “or”) should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the terms “include” and “comprise” are used synonymously. [0059] The phrase “at least one of” when followed by a list of items or elements refers to an open ended set of one or more of the elements in the list, which may but does not necessarily include more than one of the elements. Exemplary Antibodies [0060] In some embodiments, a conjugate as described herein comprises an antibody. In some such embodiments, the antibody comprises one or more antigen binding domains and an Fc domain, wherein each antigen binding domain specifically binds to an antigen. An antibody can have, for example, a first antigen binding domain that specifically binds to a first antigen, a second antigen binding domain that specifically binds to a second antigen, and an Fc domain. In various embodiments, an antibody can include two antigen binding domains, in which each antigen binding domain recognizes the same epitope on the antigen. An antibody can include two antigen binding domains in which each antigen binding domain recognizes a different epitope of the same antigen. An antibody can include two antigen binding domains in which each antigen binding domain recognizes different antigens. In various embodiments, an antibody has one antigen binding domain. In various embodiments, an antigen binding domain may comprise, for example, a heavy chain variable domain (VH) and a light chain variable domain (VL), or in the case of a heavy-chain only antibody, a V_HH. [0061] Nonlimiting exemplary tumor antigens that may be bound by a polypeptide, such as an antibody, include CD5, CD25, CD37, CD33, CD45, BCMA, CS-1, PD-L1, B7-H3, B7-DC (PD-L2), HLD-DR, carcinoembryonic antigen (CEA), TAG-72, EpCAM, MUC1, folate-binding protein (FOLR1), A33, G250 (carbonic anhydrase IX), prostate-specific membrane antigen (PSMA), GD2, GD3, GM2, Ley, CA-125, CA19-9 (MUC1 sLe(a)), epidermal growth factor, HER2, IL-2 receptor, EGFRvIII (de2-7 EGFR), fibroblast activation protein (FAP), a tenascin, a metalloproteinase, endosialin, avB3, LMP2, EphA2, PAP, AFP, ALK, polysialic acid, TRP-2, fucosyl GM1, mesothelin (MSLN), PSCA, sLe(a), GM3, BORIS, Tn, TF, GloboH, STn, CSPG4, AKAP-4, SSX2, Legumain, Tie 2, Tim 3, VEGFR2, PDGFR-B, ROR2, TRAIL1, MUC16, EGFR, CMET, HER3, MUC1, MUC15, CA6, NAPI2B, CLDN18.2, RON, LY6E, FRAlpha, DLL3, PTK7, LIV1, ROR1, CLDN6, GPC3, ADAM12, LRRC15, CDH6, TMEFF2, TMEM238, GPNMB, ALPPL2, UPK1B, UPK2, LAMP-1, LY6K, EphB2, STEAP, ENPP3, CDH3, Nectin4, LYPD3, EFNA4, GPA33, SLITRK6, and HAVCR1. [0062] In certain embodiments, the tumor antigen is selected from HER2, Nectin4, MSLN, LIV-1, MUC16, CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, CEACAM8, CEACAM16, CEACAM18, CEACAM19, CEACAM20, CEACAM21, VEGFR1, VEGFR2, MUC1, PSMA, PSA, MUC-2, and LRRC15. [0063] In certain embodiments, a polypeptide, such as an antibody, specifically binds to a non-proteinaceous or glycoantigen, such as GD2, GD3, GM2, Ley, polysialic acid, fucosyl GM1, GM3, Tn, STn, sLe(animal), or GloboH. [0064] In certain embodiments, a polypeptide, such as an antibody, specifically binds to a solid tumor antigen. In some embodiments, the solid tumor antigen is preferentially present on sarcoma or carcinoma cell(s). In some embodiments, the solid tumor antigen is preferentially present on a sarcoma cell(s). In some embodiments, the solid tumor antigen is preferentially present on a carcinoma cell(s). [0065] In some embodiments, the solid tumor antigen is present on cells of a brain, breast, lung, liver, kidney, pancreatic, colorectal, ovarian, head and neck, bone, skin, mesothelioma, bladder, stomach, prostate, thyroid, uterine or cervical/endometrial cancer. [0066] In some embodiments, the solid tumor antigen is an antigen present on breast cancer, such as HER2, LIV-1, CDH3 (p-cadherin), MUC1, Sialo-epitope CA6, PTK7, GPNMB, LAMP-1, LRRC15, ADAM12, EPHA2, TNC, LYPD3, EFNA4, Nectin-4, and CLDN6. [0067] In some embodiments, the solid tumor antigen is an antigen present on brain cancer, such as EGFRvIII, TNC and DLL-3. [0068] In some embodiments, the solid tumor antigen is an antigen present on lung cancer, such as mesothelin, HER2, EGFR, PD-L1, MSLN, LY6K, CD56, PTK7, FOLR1, DLL3, SLC34A2, CECAM5, MUC16, LRRC15, ADAM12, EGFRvIII, LYPD3, EFNA4, Nectin-4, and MUC1. [0069] In some embodiments, the solid tumor antigen is an antigen present on liver cancer, such as GPC3, EPCAM, and CECAM5. [0070] In some embodiments, the solid tumor antigen is an antigen present on kidney cancer, such as HAVCR1, ENPP3, CDH6, CD70, and cMET. [0071] In some embodiments, the solid tumor antigen is an antigen present on pancreatic cancer, such as PTK7, MUC16, MSLN, LRRC15, ADAM12, EFNA4, MUC5A, Nectin-4, and MUC1. [0072] In some embodiments, the solid tumor antigen is an antigen present on colorectal cancer, such as EPHB2, TMEM238, CECAM5, LRRC15, Nectin4, ADAM12, EFNA4 and GPA33. [0073] In some embodiments, the solid tumor antigen is an antigen present on ovarian cancer, such as MUC16, MUC1, MSLN, FOLR1, sTN, VTCN1, HER2, PTK7, FAP, TMEM238, LRRC15, CLDN6, SLC34A2 and EFNA4. [0074] In some embodiments, the solid tumor antigen is an antigen present on head and neck cancer, such as LY6K, PTK7, LRRC15, ADAM12, LYPD3, Nectin4, EFNA4 and TNC. [0075] In some embodiments, the solid tumor antigen is an antigen present on bone cancer, such as EPHA2, LRRC15, ADAM12, GPNMB, TP-3 and CD248. [0076] In some embodiments, the solid tumor antigen is an antigen present on mesothelioma, such as MSLN. [0077] In some embodiments, the solid tumor antigen is an antigen present on bladder cancer, such as LY6K, PTK7, UPK1B, UPK2, TNC, Nectin4, SLITRK6, LYPD3, EFNA4 and HER2. [0078] In some embodiments, the solid tumor antigen is an antigen present on stomach/gastric cancer, such as HER2, EPHB2, TMEM238, CECAM5 and EFNA4. [0079] In some embodiments, the solid tumor antigen is an antigen present on prostate cancer, such as PSMA, FOLH1, PTK7, STEAP, TMEFF2 (TENB2), OR51E2, SLC30A4 and EFNA4. [0080] In some embodiments, the solid tumor antigen is an antigen present on thyroid cancer, such as PTK7. [0081] In some embodiments, the solid tumor antigen is an antigen present on uterine cancer, such as present on uterine cancer such as LY6K, PTK7, EPHB2, FOLR1, ALPPL2, MUC16, Nectin-4, and EFNA4. [0082] In some embodiments, the solid tumor antigen is an antigen present on cervical/endometrial cancer, such as LY6K, PTK7, MUC16, LYPD3, EFNA4, Nectin- 4, and MUC1. [0083] In some embodiments, the solid tumor antigen is an antigen present on a sarcoma, such as LRRC15. [0084] In some embodiments, the tumor antigen is HER2. In some aspects, the HER2 antigen is expressed for example, on a lung, colorectal, ovarian, bladder, stomach/gastric, or breast cancer cell. [0085] In some aspects, the antigen is a liver cell antigen. In some aspects, the liver cell antigen is expressed on a canalicular cell, Kupffer cell, hepatocyte, or any combination thereof. In some aspects, the liver cell antigen is a hepatocyte antigen. In some aspects, the liver cell antigen is selected from the group consisting of ASGR1 (asialoglycoprotein receptor 1), ASGR2 (asialoglycoprotein receptor 2), TRF2, UGT1A1, SLC22A7, SLC13A5, SLC22A1, and C9. In some aspects, the liver cell antigen is selected from the group consisting of ASGR1, ASGR2, and TRF2. In some aspects, the liver cell antigen is expressed on a liver cell infected with a virus selected from the group consisting of HBV and HCV. [0086] In some aspects, the antigen is a viral antigen from a virus selected from the group consisting of HBV and HCV. In some aspects, the viral antigen is an HBV antigen. In some aspects, the viral antigen is HBsAg, HBcAg, or HBeAg. In some aspects, the viral antigen is HBsAg. [0087] In some embodiments, an antibody comprises an antigen binding domain and an Fc domain. In some embodiments, an antibody comprises two light chain polypeptides (light chains) and two heavy chain polypeptides (heavy chains), held together covalently by disulfide linkages. The heavy chain typically comprises a heavy chain variable region (VH) and a heavy chain constant region. The heavy chain constant region comprises three domains, CH1, CH2, and CH3. An Fc domain typically comprises heavy chain CH2 and CH3 domains. The light chain typically comprises a light chain variable region (VL) and a light chain constant region. The antigen-recognition regions of the antibody variable domains typically comprise six complementarity determining regions (CDRs), or hypervariable regions, that lie within the framework of the heavy chain variable region and light chain variable region at the N-terminal ends of the two heavy and two light chains. The constant domains provide the general framework of the antibody and may not be involved directly in binding the antibody to an antigen, but can be involved in various effector functions, such as participation of the antibody in antibody-dependent cellular cytotoxicity (ADCC). [0088] An antibody can be any class, e.g., IgA, IgD, IgE, IgG, and IgM. Certain classes can be further divided into isotypes, e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy-chain constant regions that correspond to the different classes of immunoglobulins can be α, δ, ε, γ, and μ, respectively. The light chains can be either kappa (or κ) or lambda (or λ). [0089] In some embodiments an antigen binding domain comprises a light chain complementary determining region 1 (LCDR1), a light chain complementary determining region 2 (LCDR2), a light chain complementary determining region 3 (LCDR3), a heavy chain complementary determining region 1 (HCDR1), a heavy chain complementary determining region 2 (HCDR2), and a heavy chain complementary determining region 3 (HCDR3). In some embodiments, an antibody may be a heavy- chain only antibody, in which case the antigen binding domain comprises HCDR1, HCDR2, and HCDR3, and the antibody lacks a light chain. Unless stated otherwise, the CDRs described herein can be defined according to the IMGT (the international ImMunoGeneTics information) system. [0090] An antibody can be chimeric or humanized. Chimeric and humanized forms of non-human (e.g., murine) antibodies can be intact (full length) chimeric immunoglobulins, immunoglobulin chains or antigen binding fragments thereof (such as Fv, Fab, Fabʹ, F(abʹ)₂ or other target-binding subdomains of antibodies), which can contain sequences derived from non-human immunoglobulin. In general, the humanized antibody can comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin sequence. A humanized antibody can also comprise at least a portion of an immunoglobulin constant region (Fc), an Fc domain, typically that of a human immunoglobulin sequence. [0091] An antibody described herein can be a human antibody. As used herein, “human antibodies” can include antibodies having, for example, the amino acid sequence of a human immunoglobulin and include antibodies isolated from human immunoglobulin libraries or from animals transgenic for one or more human immunoglobulins and that typically do not express endogenous immunoglobulins. Human antibodies can be produced using transgenic mice which are incapable of expressing functional endogenous immunoglobulins, but which can express human immunoglobulin genes. Completely human antibodies that recognize a selected epitope can be generated using guided selection. In this approach, a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope [0092] An antibody described herein can be a bispecific antibody or a dual variable domain antibody (DVD). Bispecific and DVD antibodies are monoclonal, often human or humanized, antibodies that have binding specificities for at least two different antigens. [0093] An antibody described herein can be derivatized or otherwise modified. For example, derivatized antibodies can be modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, or the like. [0094] An antibody described herein can specifically bind to a cancer antigen. An antibody can specifically bind to a solid tumor antigen. [0095] In some embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from trastuzumab, cetuximab, panitumumab, ofatumumab, belimumab, ipilimumab, pertuzumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, MDX-1105 (PCT Publication No. WO 2007/005874), dacetuzumab, urelumab, MPDL3280A, lambrolizumab, blinatumomab, nimotuzumab, zalutumumab, onartuzumab, patritumab, clivatuzumab, sofituzumab, edrecolomab, adecatumumab, anetumab, huDS6, lifastuzumab, PR1A3, humanized PR1A3, humanized Ab2-3, claudiximab, AMG595, ABT806, sibrotuzumab, DS-8895a variant 1, DS-8895a variant 2, MEDI-547, narnatumab, RG7841, farletuzumab, mirvetuximab, J591 variant 1, J591 variant 2, rovalpituzumab, PF-06647020, ladiratuzumab, cirmtuzumab, ladiratuzumab, huLiv1-14 (PCT Publication No. WO 2012/078688), Liv1-1.7A4 (US Patent Publication No.2011/0117013), huLiv1-22 (PCT Publication No. WO 2012078688), 4H11 (US Patent Publication No.2013/0171152), 4H5 (US Patent Publication No.2013/0171152), glembatumumab, oportuzumab, enfortumab, depatuxizumab, the antibody of ASG-15ME, huM25 (PCT Publication No. WO₂017/095808A1), and codrituzumab. [0096] In some embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), the antigen binding fragment (e.g., variable regions), or the entire heavy and light chains of an antibody selected from pertuzumab, trastuzumab, and ladiratuzumab, or biosimilar thereof. [0097] In some such embodiments, the anti-HER2 antibody of the conjugate comprises heavy chain (HC)-CDR1, HC-CDR2, HC-CDR3, light chain (LC)-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively. In further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain and light chain, wherein: (a) the heavy chain comprises HC-CDR1, HC-CDR2, and HC-CDR3 of SEQ ID NOs: 1-3, respectively, and comprises a heavy chain variable region (V_H) having an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the VH amino acid sequence of SEQ ID NO: 7; and (b) the light chain comprises LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 4-6, respectively, and a light chain variable region (V_L) having an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the VL amino acid sequence of SEQ ID NO: 8. In still further embodiments, the anti- HER2 antibody of the conjugate comprises a V_H comprising or consisting of the amino acid sequence of SEQ ID NO: 7 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 8. In yet further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain and light chain, wherein: (a) the heavy chain comprises HC-CDR1, HC-CDR2, and HC-CDR3 of SEQ ID NOs: 1-3, respectively, and comprises an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the heavy chain amino acid sequence of SEQ ID NO: 9; and (b) the light chain comprises LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 4-6, respectively, and an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the light chain amino acid sequence of SEQ ID NO: 10. In more embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain comprising or consisting of the amino acid sequence of SEQ ID NO: 9 and a light chain comprising or consisting of the amino acid sequence of SEQ ID NO: 10. [0098] In some embodiments, the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10. [0099] In some embodiments, an antibody specifically binds to a breast cancer antigen. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from trastuzumab, pertuzumab, ladiratuzumab, huLiv1-14 (PCT Publication No. WO 2012/078688), Liv1-1.7A4 (US Patent Publication No.2011/0117013), huLiv1-22 (PCT Publication No. WO 2012078688), huDS6, glembatumumab, PF-0664720, MEDI-547, DS-8895a variant 1, and DS- 08895a variant 2. [0100] In some embodiments, an antibody specifically binds to an antigen present on brain cancer cells. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from AMG595, ABT806, rovalpituzumab or depatuxizumab. [0101] In some embodiments, an antibody specifically binds to an antigen present on lung cancer cells. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from panitumumab, cetuximab, pembrolizumab, nivolumab, atezolizumab, nimotuzumab, lifastuzumab, anetumab, PF- 0664720, farletuzumab, rovalpituzumab, lifastuzumab, sofituzumab, huDS6, ABT806, AMG595, and huM25 (PCT Publication No. WO₂017/095808A1). [0102] In some embodiments, an antibody specifically binds to an antigen present on liver cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from codrituzumab, oportuzumab, and humanized PR1A3. [0103] In some embodiments, an antibody specifically binds to an antigen present on kidney cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from AGS-16M8F, AGS-16C3, the antibody of CDX-014, and onartuzumab. [0104] In some embodiments, an antibody specifically binds to an antigen present on pancreatic cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from PF-0664720, clivatuzumab, 4H11 (US Patent Publication No.2013/0171152), 4H5 (US Patent Publication No.2013/0171152), anetumumab, huDS6, sofituzumab, huM25 (PCT Publication No. WO₂017/095808A1), and RG7841. [0105] In some embodiments, an antibody specifically binds to an antigen present on colorectal cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from huM25 (PCT Publication No. WO₂017/095808A1), PR1A3, humanized PR1A3, pantumumab, cetuximab, nimotuzumab, and zalutumumab. [0106] In some embodiments, an antibody specifically binds to an antigen present on ovarian cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from sofituzumab, 4H11 (U.S. Patent Publication No.2013/0171152, 4H5 (U.S. Patent Publication No.2013/0171152), huDS6, farletuzumab, anetumab, trastuzumab, pertuzumab, PF-0664720, sibrotuzumab, huM25 (PCT Publication No. WO₂017/095808A1), and lifastuzumab. [0107] In some embodiments, an antibody specifically binds to an antigen present on head and neck cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from cetuximab, panitumumab, nimtuzumab, PF-0664720, pantumumab, cetuximab, nimotuzumab, and zalutumumab. [0108] In some embodiments, an antibody specifically binds to an antigen present on bone cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from huM25 (PCT Publication No. WO₂017/095808A1), DS-8895a variant 1, DS-8895a variant 2, and glembatumab. [0109] In some embodiments, an antibody specifically binds to an antigen present on skin cancer. [0110] In some embodiments, an antibody specifically binds to an antigen present on mesothelioma. [0111] In some embodiments, an antibody specifically binds to an antigen present on cervical/endometrial cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from PF-0664720, anetumumab, 4H11(US Patent Publication No.2013/0171152), 4H5 (US Patent Publication No.2013/0171152), huDS6, and sofituzumab. [0112] In some embodiments, an antibody specifically binds to an antigen present on bladder cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from enfortumab, trastuzumab, pertuzumab and SLITRK6. [0113] In some embodiments, an antibody specifically binds to an antigen present on stomach/gastric cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from sofituzumab, anetumab, pertuzumab, trastuzumab, and humanized PR1A3. [0114] In some embodiments, an antibody specifically binds to an antigen present on prostate cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from mirvetuximab, J591 variant 1, and J591 variant 2. [0115] In some embodiments, an antibody specifically binds to an antigen present on thyroid cancer. [0116] In some embodiments, an antibody specifically binds to an antigen present on uterine cancer. In some such embodiments, the antibody may comprise the CDRs (such as LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 and HCDR3, according to the IMGT system), antigen binding fragment (e.g., the variable regions), or the entire heavy and light chains of an antibody selected from PF-0664720, farletuzumab, sofituzumab, 4H11(US Patent Publication No.2013/0171152, and 4H5 (US Patent Publication No.2013/0171152). [0117] In some embodiments, an antibody specifically binds to an antigen present on a sarcoma. [0118] In some embodiments, an antibody specifically binds to an antigen present on a liver cell and the subject has a viral infection (e.g., HBV or HCV). The antibody can be, for example, an antibody that binds to ASGR1 or ASGR2. Exemplary Fc domains [0119] A polypeptide, such as a fusion protein or an antibody, may comprise an Fc domain. An Fc domain is a structure that can bind to one or more Fc receptors (FcRs). In various embodiments, an Fc domain is from an IgG antibody, such as an IgG1, IgG2, or IgG4 antibody. An Fc domain typically comprises CH2 and CH3 domains of a heavy chain constant region, but may comprise more or less of the heavy chain constant region as well. [0120] An Fc domain can be a domain of an antibody that can bind to an FcR(s). FcRs are organized into classes (e.g., gamma (γ), alpha (α) and epsilon (ε)) based on the class of antibody that the FcR recognizes. The FcαR class binds to IgA and includes several isoforms, FcαRI (CD89) and FcαµR. The FcγR class binds to IgG and includes several isoforms, FcγRI (CD64), FcγRIIA (CD32a), FcγRIIB (CD32b), FcγRIIIA (CD16a), and FcγRIIIB (CD16b). An FcγRIIIA (CD16a) can be an FcγRIIIA (CD16a) F158 variant or a V158 variant. FcRs also can be FcRn receptors. [0121] Each FcγR isoform can differ in binding affinity to the Fc domain of the IgG antibody. For example, FcγRI can bind to IgG with greater affinity than FcγRII or FcγRIII. The affinity of a particular FcγR isoform to an IgG can be controlled, in part, by a glycan (e.g., oligosaccharide) at position CH284.4 of the IgG antibody. For example, fucose containing CH284.4 glycans can reduce IgG affinity for FcγRIIIA. In addition, G0 glucans can have increased affinity for FcγRIIIA due to the lack of galactose and terminal GlcNAc moiety. [0122] Binding of an Fc domain to an FcR can enhance an immune response. FcR-mediated signaling that can result from an Fc domain binding to an FcR and can lead to the maturation of immune cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can lead to the maturation of dendritic cells (DCs). FcR- mediated signaling that can result from an Fc domain binding to an FcR can lead to antibody dependent cellular cytotoxicity. FcR-mediated signaling that can result from an Fc domain binding to an FcR can lead to more efficient immune cell antigen uptake and processing. FcR-mediated signaling that can result from an Fc domain binding to an FcR can promote the expansion and activation of T cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can promote the expansion and activation of CD8+ T cells. FcR-mediated signaling that can result from an Fc domain binding to an FcR can influence immune cell regulation of T cell responses. FcR- mediated signaling that can result from an Fc domain binding to an FcR can influence dendritic cell regulation of T cell responses. FcR-mediated signaling that can result from an Fc domain binding to an FcR can influence functional polarization of T cells (e.g., polarization can be toward a TH1 cell response). [0123] An Fc domain can be modified, such as by a modification of the amino acid sequence, to alter the recognition of an FcR for the Fc domain. Such modification(s) may still allow for FcR-mediated signaling, depending on the modification. A modification can be a substitution of an amino acid at a residue of an Fc domain for a different amino acid at that residue. A modification can be an insertion or deletion of an amino acid at a residue of an Fc domain. A modification can permit binding of an FcR to a site on the Fc domain to which the FcR may not otherwise bind. A modification can increase binding affinity of an FcR to the Fc domain. A modification can decrease binding affinity of an FcR to the Fc domain. [0124] An Fc domain can be a variant of a naturally occurring Fc domain (e.g., a wild type Fc domain) and can comprise at least one amino acid change as compared to the sequence of a wild-type Fc domain. An amino acid change in an Fc domain can allow the antibody or conjugate to bind to at least one Fc receptor with greater affinity compared to a wild-type Fc domain. An amino acid change in an Fc domain can allow the antibody or conjugate to bind to at least one Fc receptor with lessor affinity compared to a wild-type Fc domain. [0125] In some embodiments, an Fc domain exhibits increased binding affinity to one or more Fc receptors. In some embodiments, an Fc domain exhibits increased binding affinity to one or more Fcgamma receptors. In some embodiments, an Fc domain exhibits increased binding affinity to FcRn receptors. In some embodiments, an Fc domain exhibits increased binding affinity to Fcgamma and FcRn receptors. In other embodiments, an Fc domain exhibits the same or substantially similar binding affinity to Fcgamma and/or FcRn receptors as compared to a wild-type Fc domain from an IgG antibody (e.g., IgG1 antibody). [0126] In some embodiments, an Fc domain exhibits decreased binding affinity to one or more Fc receptors. In some embodiments, an Fc domain exhibits decreased binding affinity to one or more Fcgamma receptors. In some embodiments, an Fc domain exhibits decreased binding affinity to FcRn receptors. In some embodiments, an Fc domain exhibits decreased binding affinity to Fcgamma and FcRn receptors. In some embodiments, an Fc domain is an Fc null domain. In some embodiments, an Fc domain exhibits decreased binding affinity to FcRn receptors, but exhibits the same or increased binding affinity to one or more Fcgamma receptors as compared to a wildtype Fc domain. In some embodiments, an Fc domain exhibits increased binding affinity to FcRn receptors, but exhibits the same or decreased binding affinity to one or more Fcgamma receptors. [0127] An Fc domain may have one or more, two or more, three or more, or four or more amino acid substitutions that decrease binding of the Fc domain to an Fc receptor. In certain embodiments, an Fc domain has decreased binding affinity for one or more of FcγRI (CD64), FcγRIIA (CD32), FcγRIIIA (CD16a), FcγRIIIB (CD16b), or any combination thereof. In order to decrease binding affinity of an Fc domain to an Fc receptor, the Fc domain may comprise one or more amino acid substitutions that reduces the binding affinity of the Fc domain to an Fc receptor. In other embodiments, an Fc domain exhibits the same or substantially similar binding affinity to one or more of FcγRI (CD64), FcγRIIA (CD32), FcγRIIIA (CD16a), FcγRIIIB (CD16b), or any combination thereof as compared to a wild-type Fc domain from an IgG antibody (e.g., IgG1 antibody). In some embodiments, an Fc domain can comprise a sequence of an IgG isoform that has been modified from the wild-type IgG sequence. In some embodiments, the Fc domain can comprise a sequence of the IgG1 isoform that has been modified from the wild-type IgG1 sequence. In some embodiments, the modification comprises substitution of one or more amino acids that reduce binding affinity of an IgG Fc domain to all Fcγ receptors. [0128] A modification can be substitution of E233, L234 and L235, such as E233P/L234V/L235A or E233P/L234V/L235A/ΔG236, according to the EU index of Kabat. A modification can be a substitution of P238, such as P238A, according to the EU index of Kabat. A modification can be a substitution of D265, such as D265A, according to the EU index of Kabat. A modification can be a substitution of N297, such as N297A, according to the EU index of Kabat. A modification can be a substitution of A327, such as A327Q, according to the EU index of Kabat. A modification can be a substitution of P329, such as P239A, according to the EU index of Kabat. [0129] In some embodiments, an IgG Fc domain comprises at least one amino acid substitution that reduces its binding affinity to FcγR1, as compared to a wild-type or reference IgG Fc domain. A modification can comprise a substitution at F241, such as F241A, according to the EU index of Kabat. A modification can comprise a substitution at F243, such as F243A, according to the EU index of Kabat. A modification can comprise a substitution at V264, such as V264A, according to the EU index of Kabat. A modification can comprise a substitution at D265, such as D265A according to the EU index of Kabat. [0130] In some embodiments, an IgG Fc domain comprises at least one amino acid substitution that increases its binding affinity to FcγR1, as compared to a wild-type or reference IgG Fc domain. A modification can comprise a substitution at A327 and P329, such as A327Q/P329A, according to the EU index of Kabat. [0131] In some embodiments, the modification comprises substitution of one or more amino acids that reduce binding affinity of an IgG Fc domain to FcγRII and FcγRIIIA receptors. A modification can be a substitution of D270, such as D270A, according to the EU index of Kabat. A modification can be a substitution of Q295, such as Q295A, according to the EU index of Kabat. A modification can be a substitution of A327, such as A237S, according to the EU index of Kabat. [0132] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain to FcγRII and FcγRIIIA receptors. A modification can be a substitution of T256, such as T256A, according to the EU index of Kabat. A modification can be a substitution of K290, such as K290A, according to the EU index of Kabat. [0133] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain to FcγRII receptor. A modification can be a substitution of R255, such as R255A, according to the EU index of Kabat. A modification can be a substitution of E258, such as E258A, according to the EU index of Kabat. A modification can be a substitution of S267, such as S267A, according to the EU index of Kabat. A modification can be a substitution of E272, such as E272A, according to the EU index of Kabat. A modification can be a substitution of N276, such as N276A, according to the EU index of Kabat. A modification can be a substitution of D280, such as D280A, according to the EU index of Kabat. A modification can be a substitution of H285, such as H285A, according to the EU index of Kabat. A modification can be a substitution of N286, such as N286A, according to the EU index of Kabat. A modification can be a substitution of T307, such as T307A, according to the EU index of Kabat. A modification can be a substitution of L309, such as L309A, according to the EU index of Kabat. A modification can be a substitution of N315, such as N315A, according to the EU index of Kabat. A modification can be a substitution of K326, such as K326A, according to the EU index of Kabat. A modification can be a substitution of P331, such as P331A, according to the EU index of Kabat. A modification can be a substitution of S337, such as S337A, according to the EU index of Kabat. A modification can be a substitution of A378, such as A378A, according to the EU index of Kabat. A modification can be a substitution of E430, such as E430, according to the EU index of Kabat. [0134] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain to FcγRII receptor and reduces the binding affinity to FcγRIIIA receptor. A modification can be a substitution of H268, such as H268A, according to the EU index of Kabat. A modification can be a substitution of R301, such as R301A, according to the EU index of Kabat. A modification can be a substitution of K322, such as K322A, according to the EU index of Kabat. [0135] In some embodiments, the modification comprises substitution of one or more amino acids that decreases binding affinity of an IgG Fc domain to FcγRII receptor but does not affect the binding affinity to FcγRIIIA receptor. A modification can be a substitution of R292, such as R292A, according to the EU index of Kabat. A modification can be a substitution of K414, such as K414A, according to the EU index of Kabat. [0136] In some embodiments, the modification comprises substitution of one or more amino acids that decreases binding affinity of an IgG Fc domain to FcγRII receptor and increases the binding affinity to FcγRIIIA receptor. A modification can be a substitution of S298, such as S298A, according to the EU index of Kabat. A modification can be substitution of S239, I332 and A330, such as S239D/I332E/A330L. A modification can be substitution of S239 and I332, such as S239D/I332E. [0137] In some embodiments, the modification comprises substitution of one or more amino acids that decreases binding affinity of an IgG Fc domain to FcγRIIIA receptor. A modification can be substitution of F241 and F243, such as F241S/F243S or F241I/F243I, according to the EU index of Kabat. [0138] In some embodiments, the modification comprises substitution of one or more amino acids that decreases binding affinity of an IgG Fc domain to FcγRIIIA receptor and does not affect the binding affinity to FcγRII receptor. A modification can be a substitution of S239, such as S239A, according to the EU index of Kabat. A modification can be a substitution of E269, such as E269A, according to the EU index of Kabat. A modification can be a substitution of E293, such as E293A, according to the EU index of Kabat. A modification can be a substitution of Y296, such as Y296F, according to the EU index of Kabat. A modification can be a substitution of V303, such as V303A, according to the EU index of Kabat. A modification can be a substitution of A327, such as A327G, according to the EU index of Kabat. A modification can be a substitution of K338, such as K338A, according to the EU index of Kabat. A modification can be a substitution of D376, such as D376A, according to the EU index of Kabat. [0139] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain to FcγRIIIA receptor and does not affect the binding affinity to FcγRII receptor. A modification can be a substitution of E333, such as E333A, according to the EU index of Kabat. A modification can be a substitution of K334, such as K334A, according to the EU index of Kabat. A modification can be a substitution of A339, such as A339T, according to the EU index of Kabat. A modification can be substitution of S239 and I332, such as S239D/I332E. [0140] In some embodiments, the modification comprises substitution of one or more amino acids that increases binding affinity of an IgG Fc domain to FcγRIIIA receptor. A modification can be substitution of L235, F243, R292, Y300 and P396, such as L235V/F243L/R292P/Y300L/P396L (IgG1VLPLL) according to the EU index of Kabat. A modification can be substitution of S298, E333 and K334, such as S298A/E333A/K334A, according to the EU index of Kabat. A modification can be substitution of K246, such as K246F, according to the EU index of Kabat. [0141] Other substitutions in an IgG Fc domain that affect its interaction with one or more Fcγ receptors are disclosed in U.S. Patent Nos.7,317,091 and 8,969,526 (the disclosures of which are incorporated by reference herein). [0142] In some embodiments, an IgG Fc domain comprises at least one amino acid substitution that reduces the binding affinity to FcRn, as compared to a wild-type or reference IgG Fc domain. A modification can comprise a substitution at H435, such as H435A according to the EU index of Kabat. A modification can comprise a substitution at I253, such as I253A according to the EU index of Kabat. A modification can comprise a substitution at H310, such as H310A according to the EU index of Kabat. A modification can comprise substitutions at I253, H310 and H435, such as I253A/H310A/H435A according to the EU index of Kabat. [0143] A modification can comprise a substitution of one amino acid residue that increases the binding affinity of an IgG Fc domain for FcRn, relative to a wildtype or reference IgG Fc domain. A modification can comprise a substitution at V308, such as V308P according to the EU index of Kabat. A modification can comprise a substitution at M428, such as M428L according to the EU index of Kabat. A modification can comprise a substitution at N434, such as N434A according to the EU index of Kabat or N434H according to the EU index of Kabat. A modification can comprise substitutions at T250 and M428, such as T250Q and M428L according to the EU index of Kabat. A modification can comprise substitutions at M428 and N434, such as M428L and N434S, N434A or N434H according to the EU index of Kabat. A modification can comprise substitutions at M252, S254 and T256, such as M252Y/S254T/T256E according to the EU index of Kabat. A modification can be a substitution of one or more amino acids selected from P257L, P257N, P257I, V279E, V279Q, V279Y, A281S, E283F, V284E, L306Y, T307V, V308F, Q311V, D376V, and N434H. Other substitutions in an IgG Fc domain that affect its interaction with FcRn are disclosed in U.S. Patent No.9,803,023 (the disclosure of which is incorporated by reference herein). [0144] In some embodiments, an antibody is a human IgG2 antibody, including an IgG2 Fc region. In some embodiments, the heavy chain of the human IgG2 antibody can be mutated at cysteines at positions 127, 232, or 233. In some embodiments, the light chain of a human IgG2 antibody can be mutated at a cysteine at position 214. The mutations in the heavy and light chains of the human IgG2 antibody can be from a cysteine residue to a serine residue. Immune-Stimulatory Compounds [0145] The antibodies are attached to immune stimulatory compounds, typically via a linker(s) to form immune-stimulatory conjugates. An antibody can be attached to one or more immune-stimulatory compounds, typically from about 1 to about 10 compounds per antibody. [0146] In some embodiments, an immune stimulatory compound activates human immune cells, including but not limited to dendritic cells, macrophages, monocytes, myeloid-derived suppressor cells, NK cells, B cells, T cells, or tumor cells, or a combination thereof. In some embodiments, an immune-stimulatory compound is a myeloid cell agonist. A myeloid cell agonist is a compound that activates or stimulates an immune response by a myeloid cell. For example, a myeloid cell agonist can stimulate an immune response by causing the release of cytokines by myeloid cells, which results in the activation of immune cells. The stimulation of an immune response by a myeloid cell agonist can be measured in vitro by co-culturing immune cells (e.g., peripheral blood mononuclear cells (PBMCs)) with cells targeted by the conjugate and measuring cytokine release, chemokine release, proliferation of immune cells, upregulation of immune cell activation markers, ADCC, or any combination thereof. Exemplary assays are described in the Examples. ADCC can be measured by determining the percentage of remaining target cells in the co-culture after administration of the conjugate with the target cells and PBMCs. [0147] In general, an immune stimulatory compound acts on toll like receptors (TLRs), nucleotide-oligomerization domain-like receptors (NOD), RIG-I-Like receptors (RLR), C-type lectin receptors (CLR), or cytosolic DNA Sensors (CDS), or a combination thereof. [0148] In some embodiments, an immune stimulatory compound comprises a ligand of one or more TLRs selected from the group consisting of: TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, TLR7/TLR8, TLR9, and TLR10. [0149] In some embodiments, an immune-stimulatory compound is a myeloid cell agonist. In some embodiments, a myeloid cell agonist is a ligand of TLR2 selected from the group consisting of: (a) a heat killed bacteria product, preferably HKAL, HKEB, HKHP, HKLM, HKLP, HKLR, HKMF, HKPA, HKPG, or HKSA, HKSP, and (b) a cell-wall components product, preferably LAM, LM, LPS, LIA, LIA, PGN, FSL, Pam2CSK4, Pam3CSK4, or Zymosan. [0150] In some embodiments, a myeloid cell agonist is a ligand of TLR3 selected from the group consisting of: rintatolimod, poly-ICLC, RIBOXXON®, Apoxxim, RIBOXXIM®, IPH-33, MCT-465, MCT-475, and ND-1.1. [0151] In some embodiments, a myeloid cell agonist is a ligand of TLR4 selected from the group consisting of LPS, MPLA or a pyrimido[5,4-b]indole such as those described in PCT Publication No. WO 2014/052828 (U of Cal). [0152] In some embodiments, the myeloid cell agonist is a ligand of TLR5 selected from the group consisting of: FLA and Flagellin. [0153] In some embodiments, the myeloid cell agonist is a ligand of TLR6. [0154] In certain embodiments, a myeloid cell agonist is a TLR7 agonist and/or a TLR8 agonist. In certain embodiments, the myeloid cell agonist is a TLR7 agonist. In certain embodiments, the myeloid cell agonist is a TLR8 agonist. In some embodiments, the myeloid cell agonist selectively agonizes TLR7 and not TLR8. In other embodiments, the myeloid cell agonist selectively agonizes TLR8 and not TLR7. [0155] In certain embodiments, a myeloid cell agonist is a TLR7 agonist. In certain embodiments, the TLR7 agonist is selected from an imidazoquinoline, an imidazoquinoline amine, a thiazoquinoline, an aminoquinoline, an aminoquinazoline, a pyrido[3,2-d]pyrimidine-2,4-diamine, a pyrimidine-2,4-diamine, a 2-aminoimidazole, an 1-alkyl-1H-benzimidazol-2-amine, a tetrahydropyridopyrimidine, a heteroarothiadiazide-2,2-dioxide, a benzonaphthyridine, a thieno[3,2-d]pyrimidine, a 4- amino-imidazoquinoline, an imidazo-pyridinone, an imidazo-pyrimidinone, a purine, a fused pyrimidine-lactam, an imidazo[4,5-c]quinoline-4-amine, an imidazo[4,5- c]quinoline, a pyrimidine, a benzazepine, an imidazo-pyridine, a pyrrolo-pyrimidine, a 2-amino-quinazoline, a guanosine analog, an adenosine analog, a thymidine homopolymer, an ssRNA, CpG-A, PolyG10, and PolyG3. In certain embodiments, the TLR7 agonist is selected from an imidazoquinoline, an imidazoquinoline amine, a thiazoquinoline, an aminoquinoline, an aminoquinazoline, a pyrido[3,2-d]pyrimidine- 2,4-diamine, a pyrimidine-2,4-diamine, a 2-aminoimidazole, a 1-alkyl-1H- benzimidazol-2-amine, a tetrahydropyridopyrimidine, a heteroarothiadiazide-2,2- dioxide, a benzonaphthyridine, a thieno[3,2-d]pyrimidine, a 4-amino-imidazoquinoline, an imidazo-pyridinone, an imidazo-pyrimidinone, a purine, a fused pyrimidine-lactam, an imidazo[4,5-c]quinoline-4-amine, an imidazo[4,5-c]quinoline, a pyrimidine, a benzazepine, an imidazo-pyridine, a pyrrolo-pyrimidine, and a 2-amino-quinazoline, but is other than a guanosine analog, an adenosine analog, a thymidine homopolymer, an ssRNA, CpG-A, PolyG10, and PolyG3. In some embodiments, a TLR7 agonist is a non-naturally occurring compound. Examples of TLR7 modulators include GS-9620, GSK-2245035, imiquimod, resiquimod, DSR-6434, DSP-3025, IMO-4200, MCT-465, MEDI-9197, 3M-051, SB-9922, 3M-052, Limtop, TMX-30X, TMX-202, RG-7863, RG-7795, and the TLR7 modulator compounds disclosed in US Patent Publication No. 2016/0168164 (Janssen, thieno[3,2-d]pyrimidine derivatives), US Patent Publication No.2015/0299194 (Roche, 4-amino-imidazoquinoline derivatives), US Patent Publication No.2011/0098248 (Gilead Sciences, imidazo-pyridinone, imidazo- pyrimidinone, and purine derivatives), US Patent Publication No.2010/0143301 (Gilead Sciences, fused pyrimidine-lactam derivatives), and US Patent Publication No. 2009/0047249 (Gilead Sciences, purine derivatives), and these publications are incorporated by reference herein. Further examples of TLR7 modulators include compounds disclosed in PCT Publication No. WO₂018/009916 (Stanford University/Bolt Biotherapeutics, imidazo[4,5-c]quinolin-4-amine derivatives), PCT Publication No. WO₂018/112108 (Bolt Biotherapeutics, imidazo[4,5-c]quinoline, pyrimidine, benzazepine, imidazo-pyridine, pyrrolo-pyrimidine, and purine derivatives), US Patent Publication No.2019/0055247 (Bristol-Myers Squibb, purine derivatives), PCT Publication No. PCT Publication No. WO₂018/198091 (Novartis, pyrrolo-pyrimidine derivatives), US Patent Publication No.2017/0121421 (Novartis, pyrrolo-pyrimidine derivatives), US Patent No.10,253,003 (Janssen, 2-amino- quinazoline derivatives), and US Patent No.10,233,184 (Roche, imidazo-pyrimidinone derivatives), and these publications are incorporated by reference herein. In some embodiments, a TLR7 agonist has an EC50 value of 500 nM or less by PBMC assay measuring TNFalpha or IFNgammaproduction. In some embodiments, a TLR7 agonist has an EC50 value of 100 nM or less by PBMC assay measuring TNFalpha or IFNgamma production. In some embodiments, a TLR7 agonist has an EC50 value of 50 nM or less by PBMC assay measuring TNFalpha or IFNgamma production. In some embodiments, a TLR7 agonist has an EC50 value of 10 nM or less by PBMC assay measuring TNFalpha or IFNgamma production. [0156] In certain embodiments the myeloid cell agonist is a TLR8 agonist. In certain embodiments, the TLR8 agonist is selected from the group consisting of a benzazepine, an imidazoquinoline, a thiazoloquinoline, an aminoquinoline, an aminoquinazoline, a pyrido[3,2-d]pyrimidine-2,4-diamine, a pyrimidine-2,4-diamine, a 2-aminoimidazole, an 1-alkyl-1H-benzimidazol-2-amine, a tetrahydropyridopyrimidine, a pyrido[3,2-d]pyrimidine, a dihydropyrimidinyl benzazepine carboxamide, a benzo[b]azepine, benzazepine dicarboxamide derivatives with a tertiary amide, benzazepine dicarboxamide derivatives with a secondary amide, a quinazoline, a pyrido[3,2-d]pyrimidine, a diamino-pyrimidine, an amino-quinazoline, a heterocyclic- substituted 2-amino-quinazoline, a diamino-pyrimidine, a piperidino-pyrimidine, an alkylamino-pyrimidine, an 8-substitued benzoazepine, an amino-diazepine, an amino- benzo-diazepine, an amido-indole, an amido-benzimidazole, a phenyl sulfonamide, a dihydropteridinone, a fused amino-pyrimidine, a quinazoline, a pyrido-pyrimidine, an amino-substituted benzazepine, a pyrrolo-pyridine, an imidazo-pyridine derivatives, an amino-benzazepine, and a ssRNA. In certain embodiments, a TLR8 agonist is selected from the group consisting of a benzazepine, an imidazoquinoline, a thiazoloquinoline, an aminoquinoline, an aminoquinazoline, a pyrido[3,2-d]pyrimidine-2,4-diamine, a pyrimidine-2,4-diamine, a 2-aminoimidazole, an 1-alkyl-1H-benzimidazol-2-amine, a tetrahydropyridopyrimidine, a pyrido[3,2-d]pyrimidine, a dihydropyrimidinyl benzazepine carboxamide, a benzo[b]azepine, benzazepine dicarboxamide derivatives with a tertiary amide, benzazepine dicarboxamide derivatives with a secondary amide, a quinazoline, a pyrido[3,2-d]pyrimidine, a diamino-pyrimidine, an amino-quinazoline, a heterocyclic-substituted 2-amino-quinazoline, a diamino-pyrimidine, a piperidino- pyrimidine, an alkylamino-pyrimidine, an 8-substitued benzoazepine, an amino- diazepine, an amino-benzo-diazepine, an amido-indole, an amido-benzimidazole, a phenyl sulfonamide, a dihydropteridinone, a fused amino-pyrimidine, a quinazoline, a pyrido-pyrimidine, an amino-substituted benzazepine, a pyrrolo-pyridine, an imidazo- pyridine derivatives, and an amino-benzazepine, and is other than a ssRNA. In some embodiments, a TLR8 agonist is a non-naturally occurring compound. Examples of TLR8 agonists include motolimod, selgantolimod, resiquimod, 3M-051, 3M-052, MCT-465, IMO-4200, VTX-763, VTX-1463, and the TLR8 modulator compounds disclosed in US Patent Publication No.2018/0086755 (Gilead, pyrido[3,2-d]pyrimidine derivatives), PCT Publication No. WO₂017/216054 (Roche, dihydropyrimidinyl benzazepine carboxamide derivatives), PCT Publication No. PCT Publication No. WO₂017/190669 (Shanghai De Novo Pharmatech, benzo[b]azepine derivatives), PCT Publication No. WO₂016/142250 (Roche, benzazepine dicarboxamide derivatives), PCT Publication No. WO₂017/202704 (Roche, benzazepine dicarboxamide derivatives with a tertiary amide), PCT Publication No. WO₂017/202703 (Roche, benzazepine dicarboxamide derivatives with a secondary amide), US Patent Publication No. 2017/0071944 (Gilead, quinazoline and pyrido[3,2-d]pyrimdine derivatives), US Patent Publication No.2014/0045849 (Janssen, diamino-pyrimidine derivatives), US Patent Publication No.2014/0073642 (Janssen, amino-quinazoline derivatives), PCT Publication No. WO₂014/056953 (Janssen, pyrrolo[3,2-d]pyrimidine derivatives), PCT Publication No. WO₂014/076221 (Janssen, heterocyclic substituted 2-amino- quinazoline derivatives), PCT Publication No. WO₂014/128189 (Janssen, diamino- pyrimidine derivatives), US Patent Publication No.2014/0350031 (Janssen, piperidino- pyrimidine derivatives), PCT Publication No. WO₂014/023813 (Janssen, alkyl- aminopyrimidine derivatives), US Patent Publication No.2008/0234251 (Array Biopharma, 8-substituted benzoazepine derivatives), US Patent Publication No. 2008/0306050 (Array Biopharma, amino-diazepine derivatives), US Patent Publication No.2010/0029585 (VentiRx Pharma, amino-benzazepine derivatives), US Patent Publication No.2011/0092485 (VentiRx Pharma, amino-benzazepine derivatives), US Patent Publication No.2011/0118235 (VentiRx Pharma, amino-benzazepine derivatives), US Patent Publication No.2012/0082658 (VentiRx Pharma, amino- benzazepine VTX-378), US Patent Publication No.2012/0219615 (VentiRx Pharma), US Patent Publication No.20140066432 (VentiRx Pharma, amino-benzazepine VTX- 2337), US Patent Publication No.2014/0088085 (VentiRx Pharma, amino-benzazepine and amino-benzo-diazepine derivatives), US Patent Publication No.2014/0275167 (Novira Therapeutics, amido-indole and amido-benzimidazole derivatives), and US Patent Publication No.2013/0251673 (Novira Therapeutics, phenyl sulfonamide derivatives), and these publications are incorporated by reference herein. Further examples of TLR8 modulators include compounds disclosed in US2016/0108045 (Gilead, dihydropteridinone derivatives), US Patent Publication No.2018/0065938 (Gilead, fused amino-pyrimidine derivatives), US Patent Publication No.2018/0263985 (Gilead, quinazoline and pyrido-pyrimidine derivatives), PCT Publication No. WO₂017/046112 (Roche, amino-substituted benzazepine derivatives), PCT Publication No. WO₂016/096778 (Roche, amino-substituted benzazepine derivatives), US Patent Publication No.2019/0016808 (Birdie Biopharmaceuticals, pyrrolo- or imidazo- pyridine derivatives or amino-benzazepine derivatives), and these publications are incorporated by reference herein. In some embodiments, the TLR8 agonist comprises

, wherein the structure is optionally substituted at any position other than the -NH₂ position. In some embodiments, a TLR8 agonist has an EC50 value of 500 nM or less by PBMC assay measuring TNFalpha production. In some embodiments, a TLR8 agonist has an EC50 value of 100 nM or less by PBMC assay measuring TNFalpha production. In some embodiments, a TLR8 agonist has an EC50 value of 50 nM or less by PBMC assay measuring TNFalpha production. In some embodiments, a TLR8 agonist has an EC50 value of 10 nM or less by PBMC assay measuring TNFalpha production. [0157] In some embodiments, a TLR8 agonist is a benzazepine selected from compounds provided herein. [0158] In some embodiments, a myeloid cell agonist is a ligand of TLR9 selected from the group consisting of: ODN1585, ODN1668, ODN1826, PF-3512676 (ODN2006), ODN2007, ODN2216, ODN2336, ODN2395, BB-001, BB-006, CYT- 003, IMO-2055, IMO-2125, IMO-3100, IMO-8400, IR-103, IMO-9200, agatolimod, DIMS-9054, DV-1079, DV-1179, AZD-1419, leftolimod (MGN-1703), litenimod, and CYT-003-QbGl0. [0159] In other embodiments, the myeloid agonist selectively agonizes TLR9, TLR3, TLR4, TLR2, TLR5, RIG-I, STING, cGAS, NOD1, NOD2, NOD1/NOD2, NRLP3, ALPK1, MDA5 AIM2, IRE1, or PERK. [0160] In some embodiments, a myeloid cell agonist is a ligand of TLR10. [0161] In some embodiments, a myeloid cell agonist is a ligand of a ligand of nucleotide-oligomerization domain (NOD)-like selected from the group consisting of: NOD1 agonist (C12-iE-DAP, iE-DAP, Tri-DAP), NOD2 agonist (L18-MDP, MDP, M- TriLYS, M-TriLYS-D-ASN, Murabutide, N-Glycolyl-MDP), and NOD1/NOD2 agonists (M-TriDAP, PGN). [0162] In some embodiments, a myeloid cell agonist is a ligand of one or more RIG-I-Like receptors (RLR) selected from the group consisting of: Sʹppp-dsRNA, Poly (dA:dT), Poly(dG:dC), and Poly (I:C). [0163] In some embodiments, a myeloid cell agonist is a ligand of one or more C-type lectin receptors (CLR) selected from the group consisting of: Cnrdlan AL, HKCA, HKSC, WGP, Zymosan, and Trehalose-6,6-dibehenate. [0164] In some embodiments, a myeloid cell agonist is a ligand of one or more Cytosolic DNA Sensors (CDS) selected from the group consisting of: ADU-S100, c- GMP, c-G-AMP, c-G-GMP, c-A-AMP, c-di-AMP, c-di-IMP, c-di-GMP, c-di-UMP, HSV-60, ISD, pCpG, Poly (dA:dT), Poly( dG:dC), Poly (dA),VACV-70 and ^- mangostin and the compounds disclosed in PCT Publication No. WO₂018/156625 (U of Texas), PCT Publication No. WO 2018/152453 (Eisai), PCT Publication No. WO₂018/138685 (Janssen), PCT Publication No. WO₂018/100558 (Takeda), PCT Publication No. WO₂018/098203 (Janssen), PCT Publication No. WO₂018/065360 (Biolog Life Sciences), PCT Publication No. WO₂018/060323 (Boehringer Ingelheim), PCT Publication No. PCT Publication No. WO₂018/045204 (IFM Therapeutics), PCT Publication No. PCT Publication No. WO₂018/009466 (Aduro), PCT Publication No. WO 2017/161349 (Immune Sensor), PCT Publication No. WO₂017/123669, PCT Publication No. WO₂017/123657, PCT Publication No. WO₂017/027646 (Merck), PCT Publication No. WO₂017/027645 (Merck), PCT Publication No. WO₂016/120305 (GSK), PCT Publication No. WO₂016/096174 (InvivoGen), and US Patent Publication No.2014/0341976 (Aduro). [0165] In some embodiments, the myeloid cell agonist is a ligand of an inflammasome inducer selected from the group consisting of: (a) NLRP3 inflammasome protein complex, preferably alum Crystals, ATP, CPPD Crystals, Hennozoin, MSU Crystals, Nano-Si 02, Nigericin, and (b) AIM2 inflammasome protein complex, such as Poly (dA:dT). [0166] In certain aspects, a TLR8 agonist or a TLR7 agonist is selected from Category A or Category B, respectively, as further described herein. Variables and Formula of the Compounds of Category A (TLR8 agonists) are described in the section entitled Compounds of Category A, and variables and Formula of the Compounds of Category B (TLR7 agonists) are described in the subsequent section, entitled Compounds of Category B. Formulas and variables of the Compounds of Category A and the Compounds of Category B may overlap in nomenclature, e.g., Formula IA for both Compounds of Category A and Category B; however, variables and Formula descriptions are not intended to be interchangeable between the catagories. [0167] In some aspects, the myeloid cell agonist is a benzazepine-4- carboxamide compound. In some aspects, the benzazepine-4-carboxamide compound has the structure of Formula X-1:

wherein: R¹ is C_3-7 alkyl; R² is C3-7 alkyl or C3-7 cycloalkyl-C1-7alkyl; R³ is hydrogen; R⁴ is selected from the group consisting of C_1-7 alkyl, said C_1-7 alkyl being unsubstituted or substituted by one or two groups selected from the group consisting of phenyl and heteroaryl, said heteraryl being an aromatic 5- or 6-membered ring which comprises one, two, or three atoms selected from nitrogen, oxygen, and/or sulfur; C_3-7 cycloalkyl, said C_3-7 cycloalkyl being unsubstituted or substituted by phenyl or phenylamino-C1-4 alkyl, and heterocyclyl, said heterocyclyl being a saturated 3- to 7-membered ring containing one heteroatom selected from N and O and being unsubstituted or substituted by phenyl. Structures of Formula X-1 are described, for example, in PCT Publication No. WO₂017/202703. [0168] In some aspects, the the myeloid cell agonist is a benzazepine- dicarboxamide compound. In some aspects, the benzazepine-dicarboxamide compound has the structure of Formula X-2:

wherein: R¹ is C_3-7 alkyl; R² is C_3-7 alkyl or C_3-7 cycloalkyl-C_1-7 alkyl; R³ is a heterocycle selected from

wherein X₁ is (CH₂)_m wherein m is 1 or 2; X2 is (CH2)n wherein n is 1 or 2; X₃ is (CH₂)_o wherein o is 1 or 2; X4 is (CH2)p wherein p is 1 or 2; and Z₁ is phenyl, wherein phenyl is unsubstituted or substituted by one or two groups selected from the group consisting of C1-7 alkyl, halogen, halogen-C1-7 alkyl, C_1-7 alkoxy, hydroxy-C_1-7 alkyl, amino-C_1-7 alkyl, C_1-7 alkyl-amino-C_1-7 alkyl, and di-C1-7 alkyl-amino-C1-7 alkyl; or b)

wherein X5 is (CH2)q wherein q is 1 or 2; X₆ is (CH₂)_r wherein r is 1 or 2; Y1 is a carbon or nitrogen atom; Z₂ is hydrogen; and Z3 is selected from the group consisting of hydrogen, C1-7 alkoxy, C2-7 alkenyloxy, phenyl, phenyl-C_1-7 alkyl, phenyl-C_1-7 alkyloxy, phenyl-C_1-7 alkylamino, phenylamino-C1-7 alkyl, phenylamino, wherein phenyl is unsubstituted or substituted by one or two groups selected from the group consisting of C_1-7 alkyl, halogen, halogen-C_1- 7 alkyl, C1-7 alkoxy, hydroxy-C1-7 alkyl, amino-C1-7 alkyl, C1-7 alkyl-amino-C1-7 alkyl, and di-C_1-7 alkyl-amino-C_1-7 alkyl; or

wherein X₇ is (CH₂)_s wherein s is 1 or 2; and Z4 is phenyl, wherein phenyl is unsubstituted or substituted by one or two groups selected from the group consisting of C_1-7 alkyl, halogen, halogen-C_1-7 alkyl, C1-7 alkoxy, hydroxy-C1-7 alkyl, amino-C1-7 alkyl, C1-7 alkyl-amino-C1-7 alkyl, and di-C_1-7 alkyl-amino-C_1-7 alkyl; or

wherein X₈ is (CH₂)_t wherein t is 1 or 2; and Z₅ is phenyl, wherein phenyl is unsubstituted or substituted by one or two groups selected from the group consisting of C1-7 alkyl, halogen, halogen-C1-7 alkyl, C_1-7 alkoxy, hydroxy-C_1-7 alkyl, amino-C_1-7 alkyl, C_1-7 alkyl-amino-C_1-7 alkyl, and di-C1-7 alkyl-amino-C1-7 alkyl. Compounds of Formula X-2 are described, for example, in PCT Publication No. WO₂017/202704. [0169] In some aspects, the the myeloid cell agonist is a benzazepine sulfonamide compound. In some aspects, the benzazepine sulfonamide compound has the structure of Formula X-3:

wherein R¹ and R² are the same or different and are selected from the group consisting of C_1-7 alkyl, hydroxy-C_2-7 alkyl, amino-C_2-7 alkyl, C_2-7 alkenyl, and C_3-7 alkynyl; R³ is hydrogen or C1-7 alkyl; R⁶ is hydrogen or C_1-7 alkyl; one of R⁴ and R⁵ is selected from the group consisting of hydrogen, C1-7 alkyl, halogen-C_1-7 alkyl, and C_1-7 alkoxy, and the other one of R⁴ and R⁵ is

wherein R⁷ and R⁸ are the same or different and are selected from the group consisting of hydrogen, C1-7 alkyl, halogen-C1-7 alkyl, hydroxy-C1-7 alkyl, hydroxy-C1-7 alkoxy-C_1-7 alkyl, amino-C_1-7 alkyl, C_1-7 alkyl-amino-C_1-7 alkyl, amino-C_1-7 alkoxy-C_1-7 alkyl, C1-7 alkyl-amino-C1-7 alkoxy-C1-7 alkyl, amino-C1-7 alkyl-carbonyl, and C1-7 alkyl-xamino-C_1-7 alkyl-carbonyl; or R⁷ and R⁸ together with the nitrogen atom they are attached to form a 4- to 6- membered heterocycle which is unsubstituted or substituted with a group selected from the group consisting of amino, C_1-7 alkyl-amino, hydroxy, and hydroxy-C_1-7 alkyl, and which may contain an additional N-R¹⁰ group, wherein R¹⁰ is selected from the group consisting of hydrogen, amino-C_1-7 alkyl, and C_1-7 alkyl-amino-C_1-7 alkyl; and Y is N or CR⁹; wherein R⁹ is selected from the group consisting of hydrogen, C_1-7 alkyl, and halogen-C1-7 alkyl. Compounds of Formula X-3 are described, for example, in PCT Publication No. WO₂016/096778. [0170] In some aspects, the myeloid cell agonist is a dihydropyrimidinyl benzazepine carboxamide compound. In some aspects, the dihydropyrimidinyl benzazepine carboxamide compound has the structure of Formula X-4:

wherein R¹ is C_3-7 alkyl; R² is C3-7 alkyl or C3-7 cycloalkyl-C1-7 alkyl; R³ is hydrogen or C_1-7 alkyl; R⁴ is hydrogen or C1-7 alkyl; R⁵ is selected from the group consisting of hydrogen, halogen, C_1-7 alkyl, and C1-7 alkoxy; R⁶ is selected from the group consisting of hydrogen, halogen, C_1-7 alkyl, and C1-7 alkoxy; and X is N or CR⁷, wherein R⁷ is selected from the group consisting of hydrogen, halogen, C1-7 alkyl, and C1-7 alkoxy. Compounds of Formula X-4 are described, for example, in PCT Publication No. WO₂017/216054. [0171] In some aspects, the myeloid cell agonist is a sulfinylphenyl or sulfonimidoylphenyl benzazepine compound. In some aspects, the sulfinylphenyl or sulfonimidoylphenyl benzazepine compound has the structure of Formula X-5:

wherein X is CR⁷ or N; R¹ is C3-7alkyl or C3-7cycloalkyl; R² is selected from the group consisting of C_3-7 alkyl, hydroxy-C_1-7 alkyl, C_3-7- alkynyl, amino-C1-7 alkoxy-C1-7 alkoxy-C1-7 alkyl, halogen-C1-7 alkyl, and C3-7 cycloalkyl-C_1-7 alkyl; one of R³ and R⁴ is and the other one ^{3 4}

of R and R is selected from the group consisting of hydrogen, C1-7 alkyl, and halogen; R⁵, R⁶, and R⁷ are independently from each other selected from hydrogen, C1-7 alkyl, and halogen; R⁸ is C_1-7 alkyl; and R⁹ is absent or is =N-R¹⁰, wherein R¹⁰ is selected from the group consisting of hydrogen, C1-7 alkyl, halogen-C1-7 alkyl, hydroxy-C1-7 alkyl, and hydroxy-C1-7 alkoxy- C1-7 alkyl. Compounds of Formula X-5 are described, for example, in PCT Publication No. WO₂017/046112. [0172] In some aspects, the myeloid cell agonist is a TLR modulator compound that has the structure of Formula X-6:

wherein (1) is a double bond or a single bond; (2) is a single bond or is double bond and R1 is absent; R2 and R3 are independently selected from H and lower alkyl, or R2 and R3 are connected to form a saturated carbocycle having from 3 to 7 ring members; one of R₇ and R₈ is -NR_fR_g,

, o , and the other is hydrogen; where R_f and R_g are lower alkyl or R_f and R_g together with the nitrogen to which they are attached form a saturated heterocyclic ring having 4 to 6 ring members; R₄ is -NR_cR_d or -OR₁₀; Rc and Rd are lower alkyl, where the alkyl is optionally substituted with one or more -OH; R10 is alkyl, where the alkyl is optionally substituted with one or more -OH; Z is C and (1) is a double bond, or Z is N and (1) is a single bond; Ra and Rb are independently selected from H, alkyl, alkenyl, alkynyl, and R^e, wherein the alkyl is optionally substituted with one or more -OR¹⁰, or R^e; R^e is selected from -NH2, -NH(alkyl), and -N(alkyl)₂; R¹ is absent when (2) is a double bond, or when (2) is a single bond, R¹ and one of R^a or R^b are taken together with the atoms to which they are attached to form a saturated, partially unsaturated, or unsaturated heterocycle having 5-7 ring members, and the other of R^a or R^b is hydrogen or is absent as necessary to accommodate ring unsaturation. [0173] In some aspects, the myeloid cell agonist is a TLR modulator compound that has the structure of Formula X-7:

wherein Y is CF2CF3, CF2CF7R⁶, or an aryl or heteroaryl ring, wherein said aryl and heteroaryl rings are substituted with one or more groups independently selected from alkenyl, alkynyl, Br, CN, OH, NR⁶R⁷, C(═O)R⁸, NR⁶SO₂R⁷, (C1-C6 alkyl)amino, R⁶OC(═O)CH═CH₂—, SR⁶ and SO₂R⁶, and wherein the aryl and heteroaryl rings are optionally further substituted with one or more groups independently selected from F, Cl, CF₃, CF₃O-, HCF₂O-, alkyl, heteroalkyl and ArO-; R¹, R³ and R⁴ are independently selected from H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C₁-C₆ alkyl)amino, CH₃OCH₂O-, R⁶OC(O)CH═CH₂-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶, or R³ and R⁴ together with the atom to which they are attached form a saturated or partially unsaturated carbocyclic ring, wherein the carbocyclic ring is optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C₁-C₆ alkyl)amino, CH₃OCH₂O—, R⁶OC(═O)CH═CH₂-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶; R² and R⁸ are independently selected from H, OR⁶, NR⁶R⁷, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(O)NR⁶R⁷, (C₁-C₆ alkyl)amino, CH₃OCH₂O-, R⁶OC(═O)CH═CH2-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶; R^5a, R^5b, and R^5c are independently H, F, Cl, Br, I, OMe, CH₃, CH₂F, CHF₂ or CF3; and R⁶ and R⁷ are independently selected from H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C1-C6 alkyl)amino, CH3OCH2O-, R⁶OC(O)CH═CH₂-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶, or R⁶ and R⁷ together with the atom to which they are attached form a saturated or partially unsaturated heterocyclic ring, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C1-C6alkyl)amino, CH3OCH2O-, R⁶OC(═O)CH═CH2-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶. [0174] In some aspects, the myeloid cell agonist is a TLR modulator compound that has the structure of Formula X-8:

wherein W is -C(O)-; Z is H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR⁶ or NR⁶R⁷, wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl. F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C₁-C₆ alkyl)amino, CH₃OCH₂O-, R⁶OCC═O)CH═CH2-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶; R¹, R², R³ and R⁴ are independently selected from H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C1-C6 alkyl)amino, CH3OCH2O-, R⁶OC(C═O)CH═CH₂-, NR⁶SO₂R⁷, SR₆ and SO₂R⁶, or R¹ and R² together with the atom to which they are attached form a saturated or partially unsaturated carbocyclic ring, wherein said carbocyclic ring is optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C1-C6 alkyl)amino, CH3OCH2O—, R⁶OC(═O)CH═CH2-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶, or R³ and R⁴ together are oxo; R⁵ is H, F, Cl, Br, I, OMe, CH₃, CH₂F, CHF₂, CF₃ or CF₂CF₃; R⁶ and R⁷ are independently selected from H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, and heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl cycloalkenyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C₁-C₆ alkyl)amino, CH₃OCH₂O-, R⁶OC(═O)CH═CH2-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶; or R⁶ and R⁷ together with the atom to which they are attached form a saturated or partially unsaturated heterocyclic ring, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, F, Cl, Br, I, CN, OR⁶, NR⁶R⁷, C(═O)R⁶, C(═O)OR⁶, OC(═O)R⁶, C(═O)NR⁶R⁷, (C₁-C₆ alkyl)amino, CH₃OCH₂O-, R⁶OC(═O)CH═CH₂-, NR⁶SO₂R⁷, SR⁶ and SO₂R⁶; and n is 0, 1, 2,3 or 4. [0175] Compounds of Formula X-6, X-7, and X-8 are described, for example, in U.S. Publication Nos. US2019/0016808 and U.S. Publication No.2014/0088085. [0176] In some aspects, the myeloid cell agonist is a TLR modulator compound that has the structure of Formula X-9:

wherein R¹ is C3-7alkyl or C3-7cycloalkyl; R² is selected from the group consisting of C1-7alkyl, hydroxy-C1-7alkyl, C2- 7alkenyl, C3-7alkynyl, amino-C1-7alkoxy-C1-7alkyl, amino-C1-7alkoxy-C1-7alkoxy-C1- 7alkyl, halogen-C1-7alkyl, C3-7cycloalkyl-C1-7alkyl, and phenyl-C1-7alkyl, wherein phenyl is unsubstituted or substituted by amino-C_1-7alkyl; R³ is hydrogen; R⁴ is selected from the group consisting of phenyl, said phenyl being unsubstituted or substituted by one or two groups selected from the group consisting of C1-7alkyl, halogen, halogen-C1-7alkyl, C1-7alkoxy, hydroxy-C1-7alkyl, amino-C1-7alkyl, C1-7alkyl-amino-C1-7alkyl, di-C1-7alkyl-amino-C1- ₇alkyl, amino-C_2-7alkenyl, C_1-7alkyl-amino-C_2-7alkenyl, di-C_1-7alkyl-amino-C_2-7alkenyl, amino-C_2-7alkynyl, C_1-7alkyl-amino-C_2-7alkynyl, di-C_1-7alkyl-amino-C_2-7alkynyl, benzyloxycarbonylamino-C1-7alkyl, amino-C1-7alkoxy, amino-C1-7alkoxy-C1-7alkoxy, amino-C1-7alkoxy-C1-7alkyl, amino-C1-7alkoxy-C1-7alkoxy-C1-7alkyl, C1-7alkylsulfonyl, heterocyclylcarbonyl, and phenyl-C1-7alkyl, wherein phenyl is unsubstituted or substituted by C1-7alkoxy or amino-C1-7alkyl; or heteroaryl, said heteroaryl being a 5- or 6-membered aromatic ring containing one, two, or three heteroatoms selected from N, O, or S, and being unsubstituted or substituted by one or two groups selected from the group consisting of C1-7 alkyl, halogen, halogen-C1-7 alkyl, C1-7 alkoxy, hydroxy-C1-7 alkyl, amino-C1-7 alkyl, C1-7 alkyl-amino-C1-7 alkyl, di-C1-7 alkyl-amino-C1-7 alkyl, amino-C2-7 alkenyl, C1-7 alkyl- amino-C_2-7 alkenyl, di-C_1-7 alkyl-amino-C_2-7 alkenyl, amino-C_2-7 alkynyl, C_1-7 alkyl- amino-C2-7 alkynyl, di-C1-7 alkyl-amino-C2-7 alkynyl, benzyloxycarbonylamino-C1-7 alkyl, amino-C_1-7 alkoxy, amino-C_1-7 alkoxy-C_1-7 alkoxy, amino-C_1-7 alkoxy-C_1-7 alkyl, amino-C1-7 alkoxy-C1-7 alkoxy-C1-7 alkyl, C1-7 alkylsulfonyl, heterocyclylcarbonyl, and phenyl-C_1-7 alkyl, wherein phenyl is unsubstituted or substituted by C_1-7 alkoxy or amino-C1-7 alkyl. Compounds of Formula X-9 are described, for example, in PCT Publication No. WO₂016/142250. Compounds of Category A, TLR8 Agonists [0177] In some aspects, the present disclosure provides a TLR8 agonist represented by the structure of Formula (IIA):

or a pharmaceutically acceptable salt thereof, wherein: represents an optional double bond; L¹⁰ is -X¹⁰-; L² is selected from -X²-, -X²-C1-6 alkylene-X²-, -X²-C_2-6 alkenylene-X²-, and - X²-C_2-6 alkynylene-X²-, each of which is optionally substituted on alkylene, alkenylene or alkynylene with one or more R¹²; X¹⁰ is selected from -C(O)-, and -C(O)N(R¹⁰)-*, wherein * represents where X¹⁰ is bound to R⁵; X² at each occurrence is independently selected from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, C(O)N(R¹⁰)C(O)N(R¹⁰), -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-, -S(O)₂-, -OS(O)-, -S(O)O-, -S(O), -OS(O)₂-, -S(O)₂O, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from hydrogen; and C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R⁵ is selected from unsaturated C_4-8 carbocycle; bicyclic carbocycle; and fused 5-5, fused 5-6, and fused 6-6 bicyclic heterocycle, wherein R⁵ is optionally substituted and wherein substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁵ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁰ is independently selected at each occurrence from hydrogen, -NH2, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C_3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl; wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle. [0178] In some embodiments, the compound of Formula (IIA) is represented by Formula (IIB):

or a pharmaceutically acceptable salt thereof, wherein: R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle. [0179] In some embodiments, R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OH, -OR¹⁰, -NO₂, -CN, and C_1-10 alkyl. R²⁰, R²¹, R²², and R²³ may be each hydrogen. In certain embodiments, R²¹ is halogen. In certain embodiments, R²¹ is hydrogen. In certain embodiments, R²¹ is -OR¹⁰. For example, R²¹ may be –OCH₃. [0180] In some embodiments, R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OH, -NO₂, -CN, and C_1-10 alkyl, or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle. In certain embodiments, R²⁴ and R²⁵ are each hydrogen. In other embodiments, R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-5 carbocycle, wherein substituents are selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; and C_1-10 alkyl, C2- ₁₀ alkenyl, C_2-10 alkynyl, each of which is independently optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0181] In some embodiments, R¹ is hydrogen. In some embodiments, R² is hydrogen. In some embodiments, R² is–C(O)-. [0182] In some embodiments, L¹⁰ is selected from -C(O)N(R¹⁰)-*. In certain embodiments, R¹⁰ of -C(O)N(R¹⁰)-* is selected from hydrogen and C1-6 alkyl. For example, L¹⁰ may be -C(O)NH-*. [0183] In some embodiments, R⁵ is an optionally substituted bicyclic carbocycle. In certain embodiments, R⁵ is an optionally substituted 8- to 12- membered bicyclic carbocycle. R⁵ may be an optionally substituted 8- to 12- membered bicyclic carbocycle substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In certain embodiments, R⁵ is an optionally substituted 8- to 12- membered bicyclic carbocycle substituted with one or more substituents independently selected from -OR¹⁰, -N(R¹⁰)₂, and =O. In some embodiments, R⁵ is an optionally substituted indane, and optionally substituted tetrahydronaphthalene. R⁵ may be selected from:

, any one of which is optionally substituted. For example, the R⁵ is selected from:

[0184] In some embodiments, R⁵ is an optionally substituted unsaturated C4-8 carbocycle. In certain embodiments, R⁵ is an optionally substituted unsaturated C_4-6 carbocycle. In certain embodiments, R⁵ is an optionally substituted unsaturated C4-6 carbocycle with one or more substituents independently selected from optionally substituted C_3-12 carbocycle, and optionally substituted 3- to 12-membered heterocycle. R⁵ may be an optionally substituted unsaturated C_4-6 carbocycle with one or more substituents independently selected from optionally substituted phenyl, optionally substituted 3- to 12- heterocycle, optionally substituted C_1-10 alkyl, optionally substituted C_2-10 alkenyl, and halogen. [0185] In some embodiments, R⁵ is selected from an optionally substituted fused 5-5, fused 5-6, and fused 6-6 bicyclic heterocycle. In certain embodiments, R⁵ is an optionally substituted fused 5-5, fused 5-6, and fused 6-6 bicyclic heterocycle with one or more substituents independently selected from -C(O)OR¹⁰, -N(R¹⁰)₂, -OR¹⁰, and optionally substituted C_1-10 alkyl. In certain embodiments, R⁵ is an optionally substituted fused 5-5, fused 5-6, and fused 6-6 bicyclic heterocycle substituted with -C(O)OR¹⁰. In certain embodiments, R⁵ is an optionally substituted fused 6-6 bicyclic heterocycle. For example, the fused 6-6 bicyclic heterocycle may be an optionally substituted pyridine-piperidine. In some embodiments, L¹⁰ is bound to a carbon atom of the pyridine of the fused pyridine-piperidine. In certain embodiments, R⁵ is selected from tetrahydroquinoline, tetrahydroisoquinoline, tetrahydronaphthyridine, cyclopentapyridine, and dihydrobenzoxaborole, any one of which is optionally substituted. R⁵ may be an optionally substituted tetrahydronaphthyridine. In some embodiments, R⁵ is selected from:

[0186] In some embodiments, when R⁵ is substituted, substituents on R⁵ are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In certain embodiments, the substituents on R⁵ are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle. In certain embodiments, the substituents on R⁵ are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, and -CN; and C_1-10 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -NO₂, =O, and –CN. In some embodiments, R⁵ is not substituted. [0187] In some embodiments, L² is selected from -C(O)-, and -C(O)NR¹⁰-. In some embodiments, L² is -C(O)-. In some embodiments, L² is selected from -C(O)NR¹⁰-. R¹⁰ of -C(O)NR¹⁰- may be selected from hydrogen and C_1-6 alkyl. For example, L² may be -C(O)NH-. [0188] In some embodiments, R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle and 3- to 12-membered, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In some embodiments, R⁴ is selected from: -OR¹⁰, and -N(R¹⁰)₂; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl. In certain embodiments, R⁴ is -N(R¹⁰)₂. R¹⁰ of -N(R¹⁰)₂ may be independently selected at each occurrence from optionally substituted C_1-6 alkyl. In certain embodiments, R¹⁰ of -N(R¹⁰)₂ is independently selected at each occurrence from methyl, ethyl, propyl, and butyl, any one of which is optionally substituted. For example, R⁴ may

. In certain embodiments,

. [0189] In some embodiments, R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In certain embodiments, R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle. [0190] In some embodiments, the compound of Formula (IIB) is a compound of Formula (IIC):

or a pharmaceutically acceptable salt thereof, wherein: R¹ and R² are hydrogen; L² is -C(O)-; R⁴ is -N(R¹⁰)₂; R¹⁰ is independently selected at each occurrence from hydrogen, -NH2, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L¹⁰ is -C(O)N(R¹⁰)-*, wherein * represents where L¹⁰ is bound to R⁵; and R⁵ is a fused 5-5, fused 5-6, or fused 6-6 bicyclic heterocycle, wherein R⁵ is optionally substituted and wherein substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. [0191] In certain embodiments, R¹⁰ of -N(R¹⁰)₂ is independently selected at each occurrence from methyl, ethyl, propyl, and butyl, any one of which is optionally substituted; and/or R¹⁰ of -C(O)N(R¹⁰)-* is hydrogen. [0192] In certain embodiments, R⁴ is -N(C1-4 alkyl)₂ and L¹⁰ is -C(O)N(H)-*. [0193] In certain embodiments, R⁴ is ^{10 10}

and/or R of -C(O)N(R )-* is hydrogen. [0194] In some embodiments, the compound is selected from:

, ,

and a salt of any one thereof. [0195] In some aspects, the present disclosure provides a compound represented by the structure of Formula (IIIA):

or a pharmaceutically acceptable salt thereof, wherein: represents an optional double bond; L¹¹ is -X¹¹-; L² is selected from -X²-, -X²-C_1-6 alkylene-X²-, -X²-C_2-6 alkenylene-X²-, and -X²-C_2-6 alkynylene-X²-, each of which is optionally substituted on alkylene, alkenylene or alkynylene with one or more R¹²; X¹¹ is selected from -C(O)- and -C(O)N(R¹⁰)-*, wherein * represents where X¹¹ is bound to R⁶; X² at each occurrence is independently selected from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, C(O)N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-, -S(O)₂-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)₂-, -S(O)₂O-, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from hydrogen; C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R⁶ is selected from phenyl and 5- or 6- membered heteroaryl, any one of which is substituted with one or more substituents selected from R⁷ and R⁶ is further optionally substituted by one or more additional substituents independently selected from R¹²; R⁷ is selected from -C(O)NHNH2, -C(O)NH-C1-3 alkylene-NH(R¹⁰), -C(O)CH3, -C_1-3 alkylene-NHC(O)OR¹¹, -C_1-3 alkylene-NHC(O)R¹⁰, -C_1-3 alkylene- NHC(O)NHR¹⁰, -C1-3alkylene-NHC(O)-C1-3 alkylene-R¹⁰, and a 3- to 12-membered heterocycle optionally substituted with one or more substituents independently selected from R¹²; R¹⁰ is independently selected at each occurrence from hydrogen, -NH₂, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, -C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle; R¹¹ is selected from C_3-12 carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from R¹²; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C_3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; and wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle. [0196] In some embodiments, the compound of Formula (IIIA) is represented by Formula (IIIB):

or a pharmaceutically acceptable salt thereof, wherein: R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C_3-7 carbocycle. [0197] In some embodiments, R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OH, -NO₂, -CN, and C_1-10 alkyl. In certain embodiments, R²⁰, R²¹, R²², and R²³ are each hydrogen. In some embodiments, R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OH, -NO₂, -CN, and C_1-10 alkyl, or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle. In certain embodiments, R²⁴ and R²⁵ are each hydrogen. In certain embodiments, R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-5 carbocycle. [0198] In some embodiments, R¹ is hydrogen. In some embodiments, R² is hydrogen. [0199] In some embodiments, L¹¹ is selected from –C(O)N(R¹⁰)- *. In some embodiments, R¹⁰ of -C(O)N(R¹⁰)-* is selected from hydrogen and C1-6 alkyl. For example, L¹¹ may be –C(O)NH-*. [0200] In some embodiments, R⁶ is phenyl substituted with R⁷ and R⁶ is further optionally substituted with one or more additional substituents independently selected from R¹². In some embodiments, R⁶ is selected from phenyl substituted with one or more substituents independently selected from -C(O)NHNH₂, -C(O)NH-C_1-3 alkylene- NH(R¹⁰), -C1-3 alkylene-NHC(O)R¹⁰, and -C(O)CH3; and 3- to 12-membered heterocycle, which is optionally substituted with one or more substituents selected from –OH, -N(R¹⁰)₂, –NHC(O)(R¹⁰), -NHC(O)O(R¹⁰), -NHC(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -C(O)₂R¹⁰, and -C_1-3 alkylene-(R¹⁰) and R⁶ is further optionally substituted with one or more additional substituents independently selected from R¹². For example, R⁶ may be selected from:

[0201] In some embodiments, R⁶ is selected from a 5- and 6-membered heteroaryl substituted with one or more substituents independently selected from R⁷, and R⁶ is further optionally substituted with one or more additional substituents selected from R¹². In certain embodiments, R⁶ is selected from 5- and 6-membered heteroaryl substituted with one or more substituents independently selected from -C(O)CH₃, -C_1-3 alkylene-NHC(O)OR¹⁰, -C1-3 alkylene-NHC(O)R¹⁰, -C1-3 alkylene-NHC(O)NHR¹⁰, and -C_1-3 alkylene-NHC(O) -C_1-3 alkylene-(R¹⁰); and 3- to 12-membered heterocycle, which is optionally substituted with one or more substituents selected from –OH, -N(R¹⁰)₂, –NHC(O)(R¹⁰), –NHC(O)O(R¹⁰), -NHC(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -C(O)₂R¹⁰, and -C1-3 alkylene-(R¹⁰), and R⁶ is optionally further substituted with one or more additional substituents independently selected from R¹². R⁶ may be selected from substituted pyridine, pyrazine, pyrimidine, pyridazine, furan, pyran, oxazole, thiazole, imidazole, pyrazole, oxadiazole, oxathiazole, and triazole, and R⁶ is optionally further substituted with one or more additional substituents independently selected from R¹². In some embodiments, R⁶ is substituted pyridine and R⁶ is optionally further substituted with one or more additional substituents independently selected from R¹². R⁶ may be represented as follows: In some embodiments, R⁶ is

substituted pyridine, and wherein R⁷ is -C1-3 alkylene-NHC(O)-C1-3 alkylene-R¹⁰. In certain embodiments, R⁷ is -C₁ alkylene-NHC(O)-C₁ alkylene-R¹⁰. In certain embodiments, R⁷ is -C₁ alkylene-NHC(O)-C₁ alkylene-NH₂. In some embodiments, R⁶ is selected from:

. In certain embodiments, R⁶ is

[0202] In some embodiments, L² is selected from -C(O)-, and -C(O)NR¹⁰-. In some embodiments, L² is selected from -C(O)NR¹⁰-. R¹⁰ of -C(O)NR¹⁰- may be selected from hydrogen and C1-6 alkyl. For example, L² may be -C(O)NH-. In some embodiments, L² is -C(O)-. [0203] In some embodiments, R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle and 3- to 12-membered, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, - NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In some embodiments, R⁴ is selected from: -OR¹⁰ and -N(R¹⁰)₂; and C_1-10 alkyl, C_2-10 alkenyl, C2- 1₀ alkynyl, C_3-12 carbocycle and 3- to 12-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰ -C(O)R¹⁰, - C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl. In certain embodiments, R⁴ is -N(R¹⁰)_2. R¹⁰ of -N(R¹⁰)₂ may be independently selected at each occurrence from optionally substituted C1-6 alkyl. In some embodiments, R¹⁰ of -N(R¹⁰)₂ is independently selected at each occurrence from methyl, ethyl, propyl, and butyl, any of which are optionally substituted. For example, R⁴ may be In some embodiments, -L²-R⁴ is

[0204] In some embodiments, R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C_3-10 carbocycle and 3- to 10-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In certain embodiments, R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)O R¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹ ⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-10 carbocycle and 3- to 10-membered heterocycle. [0205] In some embodiments, the compound is selected from:

5 , , and and a salt of any one thereof.

[0206] In some aspects, the present disclosure provides a compound represented by the structure of Formula (IA):

or a pharmaceutically acceptable salt thereof, wherein:

represents an optional double bond; L¹ is selected from -X¹-, -X²-C_1-6 alkylene-X²-C_1-6 alkylene-, -X²-C_2-6 alkenylene-X²-, and -X²-C_2-6 alkynylene-X²-, each of which is optionally substituted on alkylene, alkenylene or alkynylene with one or more R¹²; L² is selected from -X²-, -X²-C1-6 alkylene-X²-, -X²-C_2-6 alkenylene-X²-, and -X²-C_2-6 alkynylene-X²-, each of which is optionally substituted on alkylene, alkenylene or alkynylene with one or more R¹²; X¹ is selected from -S-*, -N(R¹⁰)-*, -C(O)O-*, -OC(O)-*, -OC(O)O-*, - C(O)N(R¹⁰)C(O)- *, -C(O)N(R¹⁰)C(O)N(R¹⁰)*, -N(R¹⁰)C(O)-*, -CR¹⁰2N(R¹⁰)C (O)-*, -N(R¹⁰)C(O)N(R¹⁰)-*, -N(R¹⁰)C(O)O-*, -OC(O)N(R¹⁰)-*, -C(NR¹⁰)-*, -N(R¹⁰)C(NR¹⁰)-*, -C(NR¹⁰)N(R¹⁰)-*, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-*, -S(O)₂-*, -OS(O)-*, -S(O)O-*, -S(O), -OS(O)₂-*, -S(O)₂O*, -N(R¹⁰)S(O)₂-*, -S(O)₂N(R¹⁰)-*, -N(R¹⁰)S(O)-*, -S(O)N(R¹⁰)-*, -N(R¹⁰)S(O)₂N(R¹⁰)-*, and -N(R¹⁰)S(O)N(R¹⁰)-*, wherein * represents where X¹ is bound to R³; X² is independently selected at each occurrence from -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, -C(O)N(R¹⁰)C(O)N(R¹⁰), -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)- , -S(O)₂-, -OS(O)-, -S(O)O-, -S(O), -OS(O)₂-, -S(O)₂O, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)- , -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from hydrogen; C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R³ is selected from optionally substituted C_3-12 carbocycle, and optionally substituted 3- to 12-membered heterocycle, wherein substituents on R³ are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R³ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, - C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁰ is independently selected at each occurrence from: hydrogen, -NH₂, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C_3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; and wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle. [0207] In some embodiments, the compound of Formula (IA) is represented by Formula (IB):

or a pharmaceutically acceptable salt thereof, wherein: R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle. [0208] In some embodiments, R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OH, -NO₂, -CN, and C_1-10 alkyl. In certain embodiments, R²⁰, R²¹, R²², and R²³ are each hydrogen. [0209] In some embodiments, R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OH, -NO₂, -CN, and C_1-10 alkyl, or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle. In some embodiments, R²⁴ and R²⁵ are each hydrogen. In some embodiments, R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-5 carbocycle. [0210] In some embodiments, R¹ is hydrogen. In some embodiments, R² is hydrogen. [0211] In some embodiments, L¹ is selected from -N(R¹⁰)C(O)-*, -S(O)₂N(R¹⁰)- *, -CR¹⁰2N(R¹⁰)C (O)-*and -X²-C1-6 alkylene-X²-C1-6 alkylene-. In some embodiments, L¹ is selected from -N(R¹⁰)C(O)-*. In certain embodiments, R¹⁰ of -N(R¹⁰)C(O)-* is selected from hydrogen and C1-6 alkyl. For example, L¹ may be -NHC(O)-*. In some embodiments, L¹ is selected from -S(O)₂N(R¹⁰)-*. In certain embodiments, R¹⁰ of -S(O)₂N(R¹⁰)-* is selected from hydrogen and C1-6 alkyl. For example, L¹ is -S(O)₂NH- *. In some embodiments, L¹ is -CR¹⁰ ₂N(R¹⁰)C(O)-*. In certain embodiments, L¹ is selected from -CH2N(H)C(O)-* and -CH(CH3)N(H)C(O)-*. [0212] In some embodiments, R³ is selected from optionally substituted C_3-12 carbocycle, and optionally substituted 3- to 12-membered heterocycle, wherein substituents on R³ are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2- 10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, - OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In certain embodiments, R³ is selected from optionally substituted C_3-12 carbocycle, and optionally substituted 3- to 12-membered heterocycle, wherein substituents on R³ are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, - N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, - NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, - C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0213] In some embodiments, R³ is selected from an optionally substituted aryl and an optionally substituted heteroaryl. In some embodiments, R³ is an optionally substituted heteroaryl. R³ may be an optionally substituted heteroaryl substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, - C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. In certain embodiments, R³ is selected from an optionally substituted 6- membered heteroaryl. For example, R³ may be an optionally substituted pyridine. In some embodiments, R³ is an optionally substituted aryl. In certain embodiments, R³ is an optionally substituted aryl substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. R³ may be an optionally substituted phenyl. In certain embodiments, R³ is selected from pyridine, phenyl, tetrahydronaphthalene, tetrahydroquinoline, tetrahydroisoquinoline, indane, cyclopropylbenzene, cyclopentapyridine, and dihydrobenzoxaborole, any one of which is optionally substituted. R³ may be selected from:

, , ,

and any one of which is optionally substit ³

uted. For example, R may be selected from:

[0214] In some embodiments, L² is selected from -C(O)-, and -C(O)NR¹⁰-. In certain embodiments, L² is -C(O)-. In certain embodiments, L² is selected from -C(O)NR¹⁰-. R¹⁰ of -C(O)NR¹⁰- may be selected from hydrogen and C_1-6 alkyl. For example, L² may be -C(O)NH-. [0215] In some embodiments, R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. [0216] In some embodiments, R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle. In some embodiments, R⁴ is selected from: -OR¹⁰, and -N(R¹⁰)₂; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl. In certain embodiments, R⁴ is -N(R¹⁰)₂. R¹⁰ of -N(R¹⁰)₂ may be independently selected at each occurrence from optionally substituted C_1-6 alkyl. In certain embodiments, R¹⁰ of -N(R¹⁰)₂ is independently selected at each occurrence from methyl, ethyl, propyl, and butyl, any one of which is optionally substituted. For example, R⁴ may

. In certain embodiments, L²-R⁴ is

[0217] In some embodiments, R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, - C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, - OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl. In some embodiments, R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, - C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, - OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle. [0218] In some embodiments, the compound is selected from:

a salt of any one thereof. [0219] In some aspects, the present disclosure provides a compound represented by the structure of Formula (IVA):

or a pharmaceutically acceptable salt thereof, wherein:

represents an optional double bond; L¹² is selected from -X³-, -X³-C1-6 alkylene-X³-, -X³-C_2-6 alkenylene-X³-, and -X³-C_2-6 alkynylene-X³-, each of which is optionally substituted on alkylene, alkenylene, or alkynylene with one or more substituents independently selected from R¹²; L²² is independently selected from -X⁴-, -X⁴-C_1-6 alkylene-X⁴-, -X⁴-C_2-6 alkenylene-X⁴-, and -X⁴-C_2-6 alkynylene-X⁴-, each of which is optionally substituted on alkylene, alkenylene, or alkynylene with one or more substituents independently selected from R¹⁰; X³ and X⁴ are independently selected at each occurrence from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, -C(O)N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-, -S(O)₂-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)₂-, -S(O)₂O-, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from L³, and hydrogen; and C_1-10 alkyl, C2- ₁₀ alkenyl, and C_2-10 alkynyl, each of which is optionally bound to L³ and each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R⁴ and R⁸ are independently selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally bound to L³ and each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ and R⁸ is optionally bound to L³ and each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N( R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁰ is independently selected at each occurrence from L³, hydrogen, -NH₂, -C(O)OCH2C6H5; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L³ is a linker moiety, wherein there is at least one occurrence of L³; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C_3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl; wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle. [0220] In some embodiments, the compound of Formula (IVA) is represented by Formula (IVB):

or a pharmaceutically acceptable salt thereof, wherein: R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴, and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle. [0221] In some embodiments, R¹ is L³. In some embodiments, R² is L³. [0222] In some embodiments, L¹² is –C(O)N(R¹⁰)-. In some embodiments, R¹⁰ of -C(O)N(R¹⁰)- is selected from hydrogen, C_1-6 alkyl, and L³. For example, L¹² may be –C(O)NH-. [0223] In some embodiments, R⁸ is an optionally substituted 5- or 6-membered heteroaryl. R⁸ may be an optionally substituted 5- or 6- membered heteroaryl, bound to L³. In some embodiments, R⁸ is an optionally substituted pyridine, bound to L³. [0224] In some embodiments, L²² is selected from -C(O)-, and -C(O)NR¹⁰-. In certain embodiments, L²² is -C(O)-. In certain embodiments, L²² is -C(O)NR¹⁰-. R¹⁰ of -C(O)NR¹⁰- may be selected from hydrogen, C1-6 alkyl, and –L³. For example, L²² may be -C(O)NH-. [0225] In some embodiments, R⁴ is selected from: -OR¹⁰, and -N(R¹⁰)₂; and C1- ₁₀ alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, aryl, and heteroaryl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl and each of which is further optionally bound to L³. In some embodiments, R⁴ is -N(R¹⁰)₂ and R¹⁰ of -N(R¹⁰)₂ is selected from L³ and hydrogen, and wherein at least one R¹⁰ of -N(R¹⁰)₂ is L³. [0226] In some aspects, the compound of Formula (IVB) is a compound of Formula (IVC):

or a pharmaceutically acceptable salt thereof, wherein: R¹ and R² are hydrogen; L²² is -C(O)-; R⁴ -N(R¹⁰)₂; R¹⁰ is independently selected at each occurrence from hydrogen, -NH2, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L¹² is -C(O)N(R¹⁰)-*, wherein * represents where L¹² is bound to R⁸; R⁸ is an optionally substituted fused 5-5, fused 5-6, or fused 6-6 bicyclic heterocycle bound to linker moiety, L³, and wherein optional substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl. [0227] In certain embodiments: R¹⁰ of -N(R¹⁰)₂ is independently selected at each occurrence from methyl, ethyl, propyl, and butyl, any one of which is optionally substituted. In certain embodiments, R¹⁰ of -C(O)N(R¹⁰)-* is hydrogen. [0228] In certain embodiments, R⁴ is -N(C_1-4 alkyl)₂ and L¹² is -C(O)N(H)-*. [0229] In certain embodiments, R⁴ is

is hydrogen. [0230] In some embodiments, the compound is further covalently bound to a linker, L³. In some embodiments, L³ is a noncleavable linker. In some embodiments, L³ is a cleavable linker. L³ may be cleavable by a lysosomal enzyme. In some embodiments, the compound is covalently attached to an antibody. In some embodiments, the antibody specifically binds to a tumor antigen. In some embodiments, the antibody comprises a target binding domain. [0231] In some embodiments, L³ is represented by the formula: , wherein: L⁴ represents the C-terminus of the peptide and L⁵ is selected from a bond, alkylene and heteroalkylene, wherein L⁵ is optionally substituted with one or more groups independently selected from R³², and RX is a reactive moiety; and R³² is independently selected at each occurrence from halogen, -OH, -CN, -O-alkyl, -SH, =O, =S, -NH2, -NO₂; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -O-alkyl, -SH, =O, =S, -NH2, -NO₂. [0232] In some embodiments, RX comprises a leaving group. In some embodiments, RX comprises a maleimide. In some embodiments, L³ is further covalently bound to an antibody. In some embodiments, the antibody is directed against a tumor antigen. In some embodiments, the antibody comprises a target binding domain. [0233] In some embodiments, L³ is represented by the formula:

, wherein L⁴ represents the C-terminal of the peptide and L⁵ is selected from a bond, alkylene and heteroalkylene, wherein L⁵ is optionally substituted with one or more groups independently selected from R³²; RX^* comprises a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody; and, R³² is independently selected at each occurrence from halogen, -OH, -CN, -O- alkyl, -SH, =O, =S, -NH2, -NO₂; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -O-alkyl, -SH, =O, =S, -NH₂, -NO₂. In some embodiments, the peptide of L³ comprises Val—Cit or Val—Ala. [0234] In some aspects, the present disclosure provides a compound or salt selected from:

,

,

and a salt of any one thereof. [0235] In some aspects, the present disclosure provides a compound or salt selected from:

, and a salt of any one thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody. [0236] In some embodiments, L³ is represented by the formula:

, wherein RX comprises a reactive moiety, and n = 0-9. In some embodiments, RX comprises a leaving group. In some embodiments, RX comprises a maleimide. In some embodiments, L³ is represented as follows:

, wherein RX^* comprises a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, and n = 0-9. [0237] In some aspects, the present disclosure provides a compound or salt selected from:

, and a salt of any one thereof. [0238] In some aspects, the present disclosure provides a compound or salt N selected from:

,

salt of any one thereof, wherein the RX^* comprises a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody. [0239] In some embodiments, RX^* comprises a succinamide moiety and is bound to a cysteine residue of an antibody. In some embodiments, RX^* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of an antibody. [0240] In some aspects, the present disclosure provides a conjugate represented by the formula:

wherein Antibody is an antibody, D is a Category A compound or salt disclosed herein, and L³ is a linker moiety. [0241] In some aspects, the present disclosure provides a conjugate represented by the formula: wherein Antibody is an antibody and D-L³

is a Category A compound or salt disclosed herein. [0242] In some aspects, the present disclosure provides a pharmaceutical composition, comprising the conjugate disclosed herein and at least one pharmaceutically acceptable excipient. [0243] In some embodiments, the average DAR of the conjugate is from about 2 to about 8, or about 1 to about 3, or about 3 to about 5. Compounds of Category B, TLR7 Agonists [0244] In some aspects, the present disclosure provides a compound represented by the structure of Formula (IA):

or a pharmaceutically acceptable salt thereof, wherein: R¹, R², R³, R⁴, and R⁵ are independently selected from hydrogen; and C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and -CN; or R³ and R¹¹ taken together form a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and –CN; R⁶ is selected from halogen, -OR²⁰, -N(R²⁰)₂, -C(O)N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -S(O)R²⁰, and -S(O)₂R²⁰; and C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and -CN; R⁷, R⁸, R⁹, and R¹⁰ are independently selected at each occurrence from hydrogen and halogen; and C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen; R¹¹ and R¹² are independently selected from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, and –CN; and C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; or R¹¹ and R¹² taken together form a C_3-6 carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and -CN; R¹³ and R¹⁴ are independently selected at each occurrence from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, and –CN; C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, - C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, - C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁵ is independently selected at each occurrence from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C1-6 alkyl, -C_1-6 haloalkyl, -O-C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle; R¹⁶ is selected from hydrogen; and C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, C1-6 alkyl, -C1-6 haloalkyl, -O-C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle; R²⁰ is independently selected at each occurrence from hydrogen; and C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-6 alkyl, -C_1-6 haloalkyl, -O-C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle; X¹ is O, S, or NR¹⁶; X² is C(O) or S(O)₂; n is 1, 2, or 3; x is 1, 2, or 3; w is 0, 1, 2, 3, or 4; and z is 0, 1, or 2. [0245] In certain embodiments, for a compound of Formula (IA), wherein X¹ is O. In certain embodiments, for a compound of Formula (IA), n is 2. In certain embodiments, for a compound of Formula (IA), x is 2. In certain embodiments, for a compound of Formula (IA), z is 0. In certain embodiments, for a compound of Formula (IA), z is 1. [0246] In certain embodiments, a compound of Formula (IA) is represented by Formula (IB):

or a pharmaceutically acceptable salt thereof, wherein R^7ʹ, R^7ʹʹ, R^8ʹ, R^8ʹʹ, R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are independently selected at each occurrence from hydrogen and halogen; and C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen. [0247] In certain embodiments, a compound of Formula (IA) is represented by Formula (IC):

or a pharmaceutically acceptable salt thereof, wherein R^7ʹ, R^7ʹʹ, R^8ʹ, R^8ʹʹ, R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are independently selected at each occurrence from hydrogen and halogen; and C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen. [0248] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R¹, R², R³, R⁴, and R⁵ are independently selected from hydrogen and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and –CN. [0249] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R¹ and R² are independently selected from hydrogen and C1-6 alkyl. In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R¹ and R² are each hydrogen. [0250] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R³ is selected from hydrogen and C1-6 alkyl optionally substituted with one or more halogens. [0251] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R³ is hydrogen. [0252] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R⁴ is selected from hydrogen and C_1-6 alkyl optionally substituted with one or more halogens. [0253] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R⁴ is hydrogen. [0254] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R⁵ is selected from hydrogen and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, - C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and –CN. In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R⁵ is hydrogen. [0255] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R⁶ is selected from halogen, -OR²⁰, and -N(R²⁰)₂; and C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, each of which is optionally substituted with one or more substituentsindependently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and – CN; and R²⁰ is independently selected at each occurrence from hydrogen; and C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C1-6 alkyl, -C1-6 haloalkyl, -O-C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0256] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R⁶ is C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰; and R²⁰ is independently selected at each occurrence from hydrogen; C_1-6 alkyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C1-6 alkyl, -C1-6 haloalkyl, -O-C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0257] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R⁶ is C1-6 alkyl substituted with -OR²⁰, and R²⁰ is selected from hydrogen and C_1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OH, and -NH2. [0258] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R^7ʹ, R^7ʹʹ, R^8ʹ, R^8ʹʹ, R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are independently selected at each occurrence from hydrogen and halogen; and C_1-6 alkyl, optionally substituted with one or more substituents independently selected from halogen. [0259] In certain embodiments, for a compound or salt of any one of Formulas (IB) or (IC), wherein R^7ʹ and R^8ʹ are each hydrogen. In certain embodiments, for a compound or salt of any one of Formulas (IB) or (IC), wherein R^7ʹʹ and R^8ʹʹ are each C_1-6 alkyl. In certain embodiments, for a compound or salt of any one of Formulas (IB) or (IC), R^7ʹʹ and R^8ʹʹ are each methyl. [0260] In certain embodiments, for a compound or salt of any one of Formulas (IB) or (IC), R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are independently selected at each occurrence from hydrogen and C1-6 alkyl. [0261] In certain embodiments, for a compound or salt of any one of Formulas (IB) or (IC), R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are each hydrogen. [0262] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R¹¹ and R¹² are independently selected from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰; and C1-6 alkyl, optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0263] In certain embodiments, for a compound or salt of any one of Formulas (IA) or (IC), R¹³ and R¹⁴ are independently selected from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰; and C_1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0264] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R³ and R¹¹ taken together form an optionally substituted 5- to 6- membered heterocycle. [0265] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), R¹¹ and R¹² taken together form an optionally substituted C3-6 carbocycle. [0266] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), X² is C(O). [0267] In certain embodiments, the compound is represented by:

or a pharmaceutically acceptable salt of any one thereof. [0268] In certain aspects, the disclosure provides a pharmaceutical composition of a compound or pharmaceutically acceptable salt of any one of Formulas (IA), (IB), or (IC), and a pharmaceutically acceptable excipient. [0269] In certain embodiments, for a compound or salt of any one of Formulas (IA), (IB), or (IC), the compound or salt is further covalently bound to a linker, L³. [0270] In certain aspects the disclosure provides a compound represented by Formula (IIA):

or a pharmaceutically acceptable salt thereof, wherein: R² and R⁴ are independently selected from hydrogen; and C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and -CN; R²¹, R²³, and R²⁵ are independently selected from hydrogen; C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and -CN; and L³; or R²³ and R¹¹ taken together form a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and –CN; and wherein one of R²¹, R²³, and R²⁵ is L³; R⁶ is selected from halogen, -OR²⁰, -N(R²⁰)₂, -C(O)N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -S(O)R²⁰, and -S(O)₂R²⁰; and C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and -CN; R⁷, R⁸, R⁹, and R¹⁰ are independently selected at each occurrence from hydrogen and halogen; and C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen; R¹¹ and R¹² are independently selected from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, and –CN; and C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; or R¹¹ and R¹² taken together form a C3-6 carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and -CN; R¹³ and R¹⁴ are independently selected at each occurrence from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁵ is independently selected at each occurrence from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C1-6 alkyl, -C_1-6 haloalkyl, -O-C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle; R¹⁶ is selected from hydrogen; and C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, C1-6 alkyl, -C1-6 haloalkyl, -O-C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle; R²⁰ is independently selected at each occurrence from hydrogen; C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C1-6 alkyl, -C1-6 haloalkyl, -O-C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle; L³ is a linker; X¹ is O, S, or NR¹⁶; X² is C(O) or S(O)₂; n is 1, 2, or 3; x is 1, 2, or 3; w is 0, 1, 2, 3, or 4; and z is 0, 1, or 2. [0271] In certain embodiments, for a compound or salt of Formula (IIA), X¹ is O. In certain embodiments, for a compound or salt of Formula (IIA), n is 2. In certain embodiments, for a compound or salt of Formula (IIA), x is 2. In certain embodiments, for a compound or salt of Formula (IIA), z is 0. In certain embodiments, for a compound or salt of Formula (IIA), z is 1. [0272] In certain embodiments, the compound of Formula (IIA) is represented by (IIB) or (IIC):

or a pharmaceutically acceptable salt thereof, wherein R^7ʹ, R^7ʹʹ, R^8ʹ, R^8ʹʹ, R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are independently selected at each occurrence from hydrogen and halogen; and C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen. [0273] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R² and R⁴ are independently selected from hydrogen and C_1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and –CN. [0274] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R² and R⁴ are independently selected from hydrogen and C1-6 alkyl. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R² and R⁴ are each hydrogen. [0275] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²³ is selected from hydrogen and C1-6 alkyl optionally substituted with one or more halogens. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²³ is hydrogen. [0276] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²¹ is selected from hydrogen and C1-6 alkyl optionally substituted with one or more halogens. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²¹ is hydrogen. [0277] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²¹ is L³. [0278] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²⁵ is selected from hydrogen and C1-6 alkyl, optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and –CN. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²⁵ is hydrogen. [0279] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²⁵ is L³. [0280] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R⁶ is selected from halogen, -OR²⁰, and -N(R²⁰)₂; and C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, -NO₂, =O, =S, =N(R²⁰), and –CN; and R²⁰ is independently selected at each occurrence from hydrogen; and C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-6 alkyl, -C_1-6 haloalkyl, -O-C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0281] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R⁶ is C_1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -S(O)R²⁰, -S(O)₂R²⁰, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰; and R²⁰ is independently selected at each occurrence from hydrogen, -NH₂, -C(O)OCH2C6H5; C1-6 alkyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-6 alkyl, -C_1-6 haloalkyl, -O-C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0282] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R⁶ is C_1-6 alkyl substituted with -OR²⁰, and R²⁰ is selected from hydrogen and C1-6 alkyl, which is optionally substituted with one or more substituents independently selected from halogen, -OH, and -NH₂. [0283] In certain embodiments, for a compound or salt of any one of Formulas (IIB) or (IIC), R^7ʹ, R^7ʹʹ, R^8ʹ, R^8ʹʹ, R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are independently selected at each occurrence from hydrogen and halogen; and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen. [0284] In certain embodiments, for a compound or salt of any one of Formulas (IIB) or (IIC), R^7ʹ and R^8ʹ are hydrogen. [0285] In certain embodiments, for a compound or salt of any one of Formulas (IIB) or (IIC), R^7ʹʹ and R^8ʹʹ are C_1-6 alkyl. [0286] In certain embodiments, for a compound or salt of any one of Formulas (IIB) or (IIC), R^7ʹʹ and R^8ʹʹ are methyl. [0287] In certain embodiments, for a compound or salt of any one of Formulas (IIB) or (IIC), R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are independently selected at each occurrence from hydrogen and C1-6 alkyl. [0288] In certain embodiments, for a compound or salt of any one of Formulas (IIB) or (IIC), R^9ʹ, R^9ʹʹ, R^10ʹ, and R^10ʹʹ are each hydrogen. [0289] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R¹¹ and R¹² are independently selected from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, and -OC(O)R²⁰; and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0290] In certain embodiments, for a compound or salt of any one of Formulas (IIA) or (IIC), R¹³ and R¹⁴ are independently selected from hydrogen, halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, and -OC(O)R²⁰; and C_1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR²⁰, -SR²⁰, -C(O)N(R²⁰)₂, -N(R²⁰)₂, -C(O)R²⁰, -C(O)OR²⁰, -OC(O)R²⁰, C_3-12 carbocycle, and 3- to 12-membered heterocycle. [0291] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R²³ and R¹¹ taken together form an optionally substituted 5- to 6-membered heterocycle. [0292] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), R¹¹ and R¹² taken together form an optionally substituted C3-6 carbocycle. [0293] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), X² is C(O). [0294] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), L³ is a cleavable linker. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), L³ is cleavable by a lysosomal enzyme. [0295] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), L³ is represented by the formula:

wherein: L⁴ represents the C-terminus of the peptide and L⁵ is selected from a bond, alkylene and heteroalkylene, wherein L⁵ is optionally substituted with one or more groups independently selected from R³⁰, and RX is a reactive moiety; and R³⁰ is independently selected at each occurrence from halogen, -OH, -CN, -O- alkyl, -SH, =O, =S, -NH₂, -NO₂; and C₁-C₁₀ alkyl, C₂-C₁₀ alkenyl, and C₂-C₁₀ alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -OH, -CN, -O-alkyl, -SH, =O, =S, -NH2, and -NO₂. [0296] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), RX comprises a leaving group. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), RX is a maleimide or an alpha-halo carbonyl. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), the peptide of L³ comprises Val-Cit or Val-Ala. [0297] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), L³ is represented by the formula:

RX comprises a reactive moiety; and n is 0-9. [0298] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), RX comprises a leaving group. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), RX is a maleimide or an alpha-halo carbonyl. In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), L³ is further covalently bound to an antibody to form a conjugate. [0299] In certain embodiments, the disclosure provides a conjugate represented by the formula:

wherein: n is 1 to 20; D is a compound or salt of any one of a Category B compound of Formulas (IA), (IB), or (IC); and L³ is a linker moiety; or D-L³ is a compound or salt of any one of a Category B compound of Formulas (IIA), (IIB), or (IIC). [0300] In certain embodiments, for a conjugate of a compound or salt of any one of Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), n is selected from 1 to 8. In certain embodiments, for a conjugate of a compound or salt of any one of Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), n is selected from 2 to 5. In certain embodiments, for a conjugate of a compound or salt of any one of Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), n is 2. [0301] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), and (IIC), -L³ is represented by the formula:

wherein: L⁴ represents the C-terminus of the peptide and L⁵ is selected from a bond, alkylene and heteroalkylene, wherein L⁵ is optionally substituted with one or more groups independently selected from R³⁰; RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein

on RX* represents the point of attachment to the residue of the antibody; and R³⁰ is independently selected at each occurrence from halogen, -OH, -CN, -O- alkyl, -SH, =O, =S, -NH2, -NO₂; and C1-C10alkyl, C2-C10alkenyl, and C2-C10alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, -OH, -CN, -O-alkyl, -SH, =O, =S, -NH2, and -NO₂. [0302] In certain embodiments, for a compound or salt of any one of Formulas (IIA), (IIB), or (IIC), RX^* is a succinamide moiety, hydrolyzed succinamide moiety or a mixture thereof and is bound to a cysteine residue of an antibody. [0303] In certain embodiments for a compound of Formulas (IIA), (IIB) and (IIC), -L³ is represented by the formula:

wherein: RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein

on RX* represents the point of attachment to the residue of the antibody; and n is 0-9. [0304] In some aspects, the present disclosure provides a conjugate represented by the following structure:

or a pharmaceutically acceptable salt thereof, wherein Ab comprises an antibody, D is a compound or salt of a Category B compound of Formula (IID):

wherein R⁴ is alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl group comprising from 1 to 8 carbons, each J is hydrogen, each U is N, each t is 2, Q is not present, the dashed line represents a point of attachment of the adjuvant to G1 , and G1 is a bond; subscript a is an integer from 1 to 40; and subscript r is an integer from 1 to 10. In certain embodiments, D has the following structure:

. In further embodiments, the conjugate has the following structure:

. Linkers [0305] The conjugates include a linker(s) that attaches an antibody to at least one immune-stimulatory compound, such as a myeloid cell agonist. A linker can be, for example, a cleavable or a non-cleavable linker. A conjugate can comprise multiple linkers. The linkers in a conjugate can be the same linkers or different linkers. [0306] As will be appreciated by skilled artisans, a linker connects an immune- stimulatory compound(s), such as a myeloid cell agonist, to the antibody by forming a covalent linkage to the compound at one location and a covalent linkage to the antibody at another location. The covalent linkages can be formed by reaction between functional groups on the linker and functional groups on the immune-stimulatory compound and on the antibody. As used herein, the expression “linker” can include (i) unattached forms of the linker that can include a functional group capable of covalently attaching the linker to an immune-stimulatory compound and a functional group capable of covalently attached the linker to an antibody; (ii) partially attached forms of the linker that can include a functional group capable of covalently attaching the linker to an antibody and that can be covalently attached to an immune-stimulatory compound, or vice versa; and (iii) fully attached forms of the linker that can be covalently attached to both an immune stimulatory compound and to an antibody. In some specific embodiments, the functional groups on a linker and covalent linkages formed between the linker and an antibody can be specifically illustrated as Rx and Rxʹ, respectively. [0307] A linker can be short or long, and cleavable or non-cleavable. A linker can contain segments that have different characteristics, such as segments of flexibility or segments of rigidity, segments of hydrophilicity, and/or segments of hydrophobicity. A linker can be chemically stable to extracellular environments, for example, chemically stable in the blood stream, and/or may include linkages that are not stable. A linker can include linkages that are designed to cleave and/or immolate or otherwise breakdown specifically or non-specifically inside cells. A cleavable linker can be sensitive to enzymes at a specific site, such as the lysosome or the extracellar space adjacent cancer cells. [0308] A cleavable linker can include a valine-citrulline peptide, a valine- alanine peptide, a phenylalanine-lysine or other peptide, such as a peptide that forms a protease recognition and cleavage site. Such a peptide-containing linker can contain a pentafluorophenyl group. A peptide-containing linker can include a succimide or a maleimide group. A peptide-containing linker can include a para aminobenzoic acid (PABA) group. A peptide-containing linker can include an aminobenzyloxycarbonyl (PABC) group. A peptide-containing linker can include a PABA or PABC group and a pentafluorophenyl group. A peptide-containing linker can include a PABA or PABC group and a succinimide group. A peptide-containing linker can include a PABA or PABC group and a maleimide group. [0309] A non-cleavable linker is generally protease-insensitive and insensitive to intracellular processes. A non-cleavable linker can include a maleimide group. A non-cleavable linker can include a succinimide group. A non-cleavable linker can be maleimido-alkyl-C(O)- linker. A non-cleavable linker can be maleimidocaproyl linker. A maleimidocaproyl linker can be N-maleimidomethylcyclohexane-1-carboxylate. A maleimidocaproyl linker can include a succinimide group. A maleimidocaproyl linker can include pentafluorophenyl group. [0310] A linker can be a combination of a maleimidocaproyl group and one or more polyethylene glycol molecules. A linker can be a maleimide-PEG4 linker. A linker can be a combination of a maleimidocaproyl linker containing a succinimide group and one or more polyethylene glycol molecules. A linker can be a combination of a maleimidocaproyl linker containing a pentafluorophenyl group and one or more polyethylene glycol molecules. A linker can contain a maleimide(s) linked to polyethylene glycol molecules in which the polyethylene glycol can allow for more linker flexibility or can be used lengthen the linker. [0311] A linker can be a (maleimidocaproyl)-(valine-alanine)-(para- aminobenzyloxycarbonyl) linker. A linker can be a (maleimidocaproyl)-(valine- citrulline)-(para-aminobenzyloxycarbonyl) linker. A linker can be a (maleimidocaproyl)-(phenylalanine-lysine)-(para-aminobenzyloxycarbonyl) linker. [0312] A linker can also contain segments of alkylene, alkenylene, alkynylene, polyether, polyester, polyamide, polyamino acids, peptides, polypeptides, cleavable peptides, and/or aminobenzyl-carbamates. A linker can contain a maleimide at one end and an N-hydroxysuccinimidyl ester at the other end. A linker can contain a lysine with an N-terminal amine acetylated, and a valine-citrulline, valine-alanine or phenylalanine- lysine cleavage site. A linker can be a link created by a microbial transglutaminase, wherein the link can be created between an amine-containing moiety and a moiety engineered to contain glutamine as a result of the enzyme catalyzing a bond formation between the acyl group of a glutamine side chain and the primary amine of a lysine chain. A linker can contain a reactive primary amine. A linker can be a Sortase A linker. A Sortase A linker can be created by a Sortase A enzyme fusing an LXPTG recognition motif (SEQ ID NO: 11) to an N-terminal GGG motif to regenerate a native amide bond. The linker created can therefore link to a moiety attached to the LXPTG recognition motif (SEQ ID NO: 11) with a moiety attached to the N-terminal GGG motif. A linker can be a link created between an unnatural amino acid on one moiety reacting with oxime bond that was formed by modifying a ketone group with an alkoxyamine on another moiety. A moiety can be part of a conjugate. A moiety can be part of an antibody, such as an antibody. A moiety can be part of an immune- stimulatory compound, such as a myeloid cell agonist. A moiety can be part of a binding domain. A linker can be unsubstituted or substituted, for example, with a substituent. A substituent can include, for example, hydroxyl groups, amino groups, nitro groups, cyano groups, azido groups, carboxyl groups, carboxaldehyde groups, imine groups, alkyl groups, alkenyl groups, alkynyl groups, alkoxy groups, acyl groups, acyloxy groups, amide groups, and ester groups. [0313] A linker can be polyvalent such that it covalently links more than one immune-stimulatory compound to a single site on the antibody, or monovalent such that it covalently links a single immune-stimulatory compound to a single site on the antibody. [0314] Exemplary polyvalent linkers that may be used to attach many immune- stimulatory compounds to an antibody of the conjugate are described. For example, Fleximer® linker technology has the potential to enable high-DAR conjugate with good physicochemical properties. As shown below, the Fleximer® linker technology is based on incorporating molecules into a solubilizing poly-acetal backbone via a sequence of ester bonds. The methodology renders highly-loaded conjugates (DAR up to 20) whilst maintaining good physicochemical properties. This methodology can be utilized with an immune-stimulatory compound as shown in the scheme below, where Drugʹ refers to the immune-stimulatory compound.

[0315] To utilize the Fleximer® linker technology depicted in the scheme above, an aliphatic alcohol can be present or introduced into the immune-stimulatory compound. The alcohol moiety is then attached to an alanine moiety, which is then synthetically incorporated into the Fleximer® linker. Liposomal processing of the conjugate in vitro releases the parent alcohol-containing drug. [0316] By way of example and not limitation, some cleavable and noncleavable linkers that may be included in the conjugates described herein are described below. [0317] Cleavable linkers can be cleavable in vitro and in vivo. Cleavable linkers can include chemically or enzymatically unstable or degradable linkages. Cleavable linkers can rely on processes inside the cell to liberate an immune- stimulatory compound, such as reduction in the cytoplasm, exposure to acidic conditions in the lysosome, or cleavage by specific proteases or other enzymes within the cell. Cleavable linkers can incorporate one or more chemical bonds that are chemically or enzymatically cleavable while the remainder of the linker can be non- cleavable. [0318] A linker can contain a chemically labile group such as hydrazone and/or disulfide group. Linkers comprising chemically labile groups can exploit differential properties between the plasma and some cytoplasmic compartments. The intracellular conditions that can facilitate immune-stimulatory compound release for hydrazine- containing linkers can be the acidic environment of endosomes and lysosomes, while disulfide-containing linkers can be reduced in the cytosol, which can contain high thiol concentrations, e.g., glutathione. The plasma stability of a linker containing a chemically labile group can be increased by introducing steric hindrance using substituents near the chemically labile group. [0319] Acid-labile groups, such as hydrazones, can remain intact during systemic circulation in the blood’s neutral pH environment (pH 7.3-7.5) and can undergo hydrolysis and can release an immune-stimulatory compound once the conjugate is internalized into mildly acidic endosomal (pH 5.0-6.5) and lysosomal (pH 4.5-5.0) compartments of the cell. This pH dependent release mechanism can be associated with nonspecific release of the immune-stimulatory compound. To increase the stability of the hydrazone group of the linker, the linker can be varied by chemical modification, e.g., substitution, allowing tuning to achieve more efficient release in the lysosome with a minimized loss in circulation. [0320] Hydrazone-containing linkers can contain additional cleavage sites, such as additional acid-labile cleavage sites and/or enzymatically labile cleavage sites. Conjugates including exemplary hydrazone-containing linkers can include, for example, the following structures:

wherein D is an immune-stimulatory compound and Ab is an antibody, respectively, and n represents the number of compound-bound linkers (LP) bound to the antibody. In certain linkers, such as linker (Ia), the linker can comprise two cleavable groups, a disulfide and a hydrazone moiety. For such linkers, effective release of the unmodified free immune-stimulatory compound can require acidic pH or disulfide reduction and acidic pH. Linkers such as (Ib) and (Ic) can be effective with a single hydrazone cleavage site. [0321] Other acid-labile groups that can be included in linkers include cis- aconityl-containing linkers. cis-Aconityl chemistry can use a carboxylic acid juxtaposed to an amide bond to accelerate amide hydrolysis under acidic conditions. [0322] Cleavable linkers can also include a disulfide group. Disulfides can be thermodynamically stable at physiological pH and can be designed to release an immune-stimulatory compound upon internalization inside cells, wherein the cytosol can provide a significantly more reducing environment compared to the extracellular environment. Scission of disulfide bonds can require the presence of a cytoplasmic thiol cofactor, such as (reduced) glutathione (GSH), such that disulfide-containing linkers can be reasonably stable in circulation, selectively releasing the immune- stimulatory compound in the cytosol. The intracellular enzyme protein disulfide isomerase, or similar enzymes capable of cleaving disulfide bonds, can also contribute to the preferential cleavage of disulfide bonds inside cells. GSH can be present in cells in the concentration range of 0.5-10 mM compared with a significantly lower concentration of GSH or cysteine, the most abundant low-molecular weight thiol, in circulation at approximately 5 µM. Tumor cells, where irregular blood flow can lead to a hypoxic state, can result in enhanced activity of reductive enzymes and therefore even higher glutathione concentrations. The in vivo stability of a disulfide-containing linker can be enhanced by chemical modification of the linker, e.g., use of steric hindrance adjacent to the disulfide bond. [0323] Immune-stimulatory conjugates including disulfide-containing linkers can include the following structures:

wherein D is an immune-stimulatory compound and Ab is an antibody, respectively, n represents the number of compounds bound to linkers bound to the antibody and R is independently selected at each occurrence from hydrogen or alkyl, for example. Increasing steric hindrance adjacent to the disulfide bond can increase the stability of the linker. Structures such as (IIa) and (IIc) can show increased in vivo stability when one or more R groups is selected from a lower alkyl such as methyl. [0324] Another type of linker that can be used is a linker that is specifically cleaved by an enzyme. For example, the linker can be cleaved by a lysosomal enzyme. Such linkers can be peptide-based or can include peptidic regions that can act as substrates for enzymes. Peptide based linkers can be more stable in plasma and extracellular milieu than chemically labile linkers. [0325] Peptide bonds can have good serum stability, as lysosomal proteolytic enzymes can have very low activity in blood due to endogenous inhibitors and the unfavorable pH value of blood compared to lysosomes. Release of an immune- stimulatory compound from an antibody can occur due to the action of lysosomal proteases, e.g., cathepsin and plasmin. These proteases can be present at elevated levels in certain tumor tissues. A linker can be cleavable by a lysosomal enzyme. The lysosomal enzyme can be, for example, cathepsin B, cathepsin S, β-glucuronidase, or β- galactosidase. [0326] The cleavable peptide can be selected from tetrapeptides such as Gly- Phe-Leu-Gly, Ala-Leu-Ala-Leu, dipeptides such as Val-Cit, Val-Ala, and Phe-Lys, or other peptides. Dipeptides can have lower hydrophobicity compared to longer peptides, depending on the composition of the peptide. [0327] A variety of dipeptide-based cleavable linkers can be used in the immune-stimulatory conjugates described herein. [0328] Enzymatically cleavable linkers can include a self-immolative spacer to spatially separate the immune-stimulatory compound from the site of enzymatic cleavage. The direct attachment of an immune-stimulatory compound to a peptide linker can result in proteolytic release of the immune-stimulatory compound or of an amino acid adduct of the immune-stimulatory compound, thereby impairing its activity. The use of a self-immolative spacer can allow for the elimination of the fully active, chemically unmodified immune-stimulatory compound upon amide bond hydrolysis. [0329] One self-immolative spacer can be a bifunctional para-aminobenzyl alcohol group (PABA), which can link to the peptide through the amino group, forming an amide bond, while amine containing immune-stimulatory compounds can be attached through carbamate functionalities to the benzylic hydroxyl group of the linker (to give a p-amidobenzylcarbamate, PABC). The resulting pro-immune-stimulatory compound can be activated upon protease-mediated cleavage, leading to a 1,6- elimination reaction releasing the unmodified immune-stimulatory compound, carbon dioxide, and remnants of the linker. The following scheme depicts the fragmentation of p- amidobenzyl carbamate and release of the immune-stimulatory compound:

wherein X-D represents the unmodified immune-stimulatory compound and the carbonyl group adjacent “peptide” is part of the peptide. Heterocyclic variants of this self-immolative group have also been described. [0330] An enzymatically cleavable linker can be a ß-glucuronic acid-based linker. Facile release of an immune-stimulatory compound can be realized through cleavage of the ß-glucuronide glycosidic bond by the lysosomal enzyme ß- glucuronidase. This enzyme can be abundantly present within lysosomes and can be overexpressed in some tumor types, while the enzyme activity outside cells can be low. ß-glucuronic acid-based linkers can be used to circumvent the tendency of an immune- stimulatory conjugate to undergo aggregation due to the hydrophilic nature of ß- glucuronides. In certain embodiments, ß-glucuronic acid-based linkers can link an antibody to a hydrophobic immune-stimulatory compound. The following scheme depicts the release of an immune-stimulatory compound (D) from an immune- stimulatory conjugate containing a ß-glucuronic acid-based linker:

wherein Ab indicates the antibody. [0331] A variety of cleavable β-glucuronic acid-based linkers useful for linking drugs such as auristatins, camptothecin and doxorubicin analogues, CBI minor-groove binders, and psymberin to antibodies have been described. These β-glucuronic acid- based linkers may be used in the conjugates described herein. In certain embodiments, the enzymatically cleavable linker is a β-galactoside-based linker. β-Galactoside is present abundantly within lysosomes, while the enzyme activity outside cells is low. [0332] Additionally, immune-stimulatory compounds containing a phenol group can be covalently bonded to a linker through the phenolic oxygen. One such linker relies on a methodology in which a diamino-ethane “Space Link” is used in conjunction with traditional “PABO”-based self-immolative groups to deliver phenols. [0333] Cleavable linkers can include non-cleavable portions or segments, and/or cleavable segments or portions can be included in an otherwise non-cleavable linker to render it cleavable. By way of example only, polyethylene glycol (PEG) and related polymers can include cleavable groups in the polymer backbone. For example, a polyethylene glycol or polymer linker can include one or more cleavable groups such as a disulfide, a hydrazone or a dipeptide. [0334] Other degradable linkages that can be included in linkers can include ester linkages formed by the reaction of PEG carboxylic acids or activated PEG carboxylic acids with alcohol groups on an immune-stimulatory compound, wherein such ester groups can hydrolyze under physiological conditions to release the immune- stimulatory compound. Hydrolytically degradable linkages can include, but are not limited to, carbonate linkages; imine linkages resulting from reaction of an amine and an aldehyde; phosphate ester linkages formed by reacting an alcohol with a phosphate group; acetal linkages that are the reaction product of an aldehyde and an alcohol; orthoester linkages that are the reaction product of a formate and an alcohol; and oligonucleotide linkages formed by a phosphoramidite group, including but not limited to, at the end of a polymer, and a 5ʹ hydroxyl group of an oligonucleotide. [0335] A linker can contain an enzymatically cleavable peptide moiety, for example, a linker comprising structural formula (IIIa), (IIIb), (IIIc), or (IIId):

or a pharmaceutically acceptable salt thereof, wherein: “peptide” represents a peptide (illustrated in N→C orientation, wherein peptide includes the amino and carboxy “termini”) that is cleavable by a lysosomal enzyme; T represents a polymer comprising one or more ethylene glycol units or an alkylene chain, or combinations thereof; R^a is selected from hydrogen, alkyl, sulfonate and methyl sulfonate; R^y is hydrogen or C_1-4 alkyl-(O)r-(C1-4 alkylene)s-G¹ or C1-4 alkyl-(N)-[(C1-4 alkylene)-G¹]2; R^z is C1-4 alkyl- (O)_r-(C_1-4 alkylene)_s-G²; G¹ is SO₃H, CO₂H, PEG 4-32, or a sugar moiety; G² is SO₃H, CO₂H, or a PEG 4-32 moiety; r is 0 or 1; s is 0 or 1; p is an integer ranging from 0 to 5; q is 0 or 1; x is 0 or 1; y is 0 or 1; represents the point of attachment of the linker to an immune-stimulatory compound; and * represents the point of attachment to the remainder of the linker. [0336] In certain embodiments, the peptide can be selected from natural amino acids, unnatural amino acids or combinations thereof. In certain embodiments, the peptide can be selected from a tripeptide or a dipeptide. In particular embodiments, the dipeptide can comprise L-amino acids and be selected from: Val-Cit; Cit-Val; Ala-Ala; Ala-Cit; Cit-Ala; Asn-Cit; Cit-Asn; Cit-Cit; Val-Glu; Glu-Val; Ser-Cit; Cit-Ser; Lys- Cit; Cit-Lys; Asp-Cit; Cit-Asp; Ala-Val; Val-Ala; Phe-Lys; Lys-Phe; Val-Lys; Lys-Val; Ala-Lys; Lys-Ala; Phe-Cit; Cit-Phe; Leu- Cit; Cit-Leu; Ile-Cit; Cit-Ile; Phe-Arg; Arg- Phe; Cit-Trp; and Trp-Cit, or salts thereof. [0337] Exemplary embodiments of linkers according to structural formula (IIIa) are illustrated below (as illustrated, the linkers include a reactive group suitable for covalently linking the linker to an antibody):

wherein indicates an attachment site of a linker to an immune-stimulatory compound. [0338] Exemplary embodiments of linkers according to structural formula (IIIb), (IIIc), or (IIId) that can be included in the conjugates described herein can include the linkers illustrated below (as illustrated, the linkers can include a reactive group suitable for covalently linking the linker to an antibody):

wherein indicates an attachment site to an immune-stimulatory compound. [0339] The linker can contain an enzymatically cleavable sugar moiety, for example, a linker comprising structural formula (IVa), (IVb), (IVc), (IVd), or (IVe):

or a pharmaceutically acceptable salt thereof, wherein: q is 0 or 1; r is 0 or 1; X¹ is CH2, O or NH; represents the point of attachment of the linker to an immune-stimulatory compound; and * represents the point of attachment to the remainder of the linker. [0340] Exemplary embodiments of linkers according to structural formula (IVa) that may be included in the immune-stimulatory conjugates described herein can include the linkers illustrated below (as illustrated, the linkers include a group suitable for covalently linking the linker to an antibody):

, wherein represents the point of attachment of a linker to an immune-stimulatory. [0341] Exemplary embodiments of linkers according to structural formula (IVb) that may be included in the conjugates described herein include the linkers illustrated below (as illustrated, the linkers include a group suitable for covalently linking the linker to an antibody):

, wherein represents the point of attachment of a linker to an immune-stimulatory compound. [0342] Exemplary embodiments of linkers according to structural formula (IVc) that may be included in the conjugates described herein include the linkers illustrated below (as illustrated, the linkers include a group suitable for covalently linking the linker to an antibody):

, wherein represents the point of attachment of a linker to an immune-stimulatory compound. [0343] Exemplary embodiments of linkers according to structural formula (IVd) that may be included in the conjugates described herein include the linkers illustrated below (as illustrated, the linkers include a group suitable for covalently linking the linker to an antibody):

, wherein represents the point of attachment of a linker to an immune-stimulatory compound. [0344] Exemplary embodiments of linkers according to structural formula (IVe) that may be included in the conjugates described herein include the linkers illustrated below (as illustrated, the linkers include a group suitable for covalently linking the linker to an antibody):

, wherein represents the point of attachment of a linker to an immune-stimulatory compound. [0345] Although cleavable linkers can provide certain advantages, the linkers comprising the conjugate described herein need not be cleavable. For non-cleavable linkers, the immune-stimulatory compound release may not depend on the differential properties between the plasma and some cytoplasmic compartments. The release of the immune-stimulatory compound can occur after internalization of the immune- stimulatory conjugate via antigen-mediated endocytosis and delivery to lysosomal compartment, where the antibody can be degraded to the level of amino acids through intracellular proteolytic degradation. This process can release an immune-stimulatory compound derivative, which is formed by the immune-stimulatory compound, the linker, and the amino acid residue or residues to which the linker was covalently attached. The immune-stimulatory compound derivative from immune-stimulatory conjugates with non-cleavable linkers can be more hydrophilic and less membrane permeable, which can lead to less bystander effects and less nonspecific toxicities compared to immune-stimulatory conjugates with a cleavable linker. Immune- stimulatory conjugates with non-cleavable linkers can have greater stability in circulation than immune-stimulatory conjugates with cleavable linkers. Non-cleavable linkers can include alkylene chains, or can be polymeric, such as, for example, based upon polyalkylene glycol polymers, amide polymers, or can include segments of alkylene chains, polyalkylene glycols and/or amide polymers. The linker can contain a polyethylene glycol segment having from 1 to 6 ethylene glycol units. [0346] The linker can be non-cleavable in vivo, for example, a linker according to the formulations below:

or salts thereof, wherein: R^a is selected from hydrogen, alkyl, sulfonate and methyl sulfonate; R^x is a reactive moiety including a functional group capable of covalently linking the linker to an antibody; and represents the point of attachment of the linker to an immune-stimulatory compound. [0347] Exemplary embodiments of linkers according to structural formula (Va)- (Vf) that may be included in the conjugates described herein include the linkers illustrated below (as illustrated, the linkers include a group suitable for covalently linking the linker to an antibody, and represents the point of attachment of the linker to an immune-stimulatory compound:

[0348] Attachment groups that are used to attach the linkers to an antibody can be electrophilic in nature and include, for example, maleimide groups, alkynes, alkynoates, allenes and allenoates, activated disulfides, active esters such as NHS esters and HOBt esters, haloformates, acid halides, alkyl, and benzyl halides such as haloacetamides. There are also emerging technologies related to “self-stabilizing” maleimides and “bridging disulfides” that can be used in accordance with the disclosure. [0349] Maleimide groups are frequently used in the preparation of conjugates because of their specificity for reacting with thiol groups of, for example, cysteine groups of the antibody of a conjugate. The reaction between a thiol group of an antibody and a drug with a linker including a maleimide group proceeds according to the following scheme:

[0350] The reverse reaction leading to maleimide elimination from a thio- substituted succinimide may also take place. This reverse reaction is undesirable as the maleimide group may subsequently react with another available thiol group such as other proteins in the body having available cysteines. Accordingly, the reverse reaction can undermine the specificity of a conjugate. One method of preventing the reverse reaction is to incorporate a basic group into the linking group shown in the scheme above. Without wishing to be bound by theory, the presence of the basic group may increase the nucleophilicity of nearby water molecules to promote ring-opening hydrolysis of the succinimide group. The hydrolyzed form of the attachment group is resistant to deconjugation in the presence of plasma proteins. So-called “self- stabilizing” linkers provide conjugates with improved stability. A representative schematic is shown below:

. [0351] The hydrolysis reaction schematically represented above may occur at either carbonyl group of the succinimide group. Accordingly, two possible isomers may result, as shown below:

[0352] The identity of the base as well as the distance between the base and the maleimide group can be modified to tune the rate of hydrolysis of the thio-substituted succinimide group and optimize the delivery of a conjugate to a target by, for example, improving the specificity and stability of the conjugate. [0353] Bases suitable for inclusion in a linker described herein, e.g., any linker described herein with a maleimide group prior to conjugating to an antibody, may facilitate hydrolysis of a nearby succinimide group formed after conjugation of the antibody to the linker. Bases may include, for example, amines (e.g., -N(R²⁶)(R²⁷), where R²⁶ and R²⁷ are independently selected from H and C_1-6 alkyl), nitrogen- containing heterocycles (e.g., a 3- to 12-membered heterocycle including one or more nitrogen atoms and optionally one or more double bonds), amidines, guanidines, and carbocycles or heterocycles substituted with one or more amine groups (e.g., a 3- to 12- membered aromatic or non-aromatic cycle optionally including a heteroatom such as a nitrogen atom and substituted with one or more amines of the type -N(R²⁶)(R²⁷), where R²⁶ and R²⁷ are independently selected from H or C_1-6 alkyl). A basic unit may be separated from a maleimide group by, for example, an alkylene chain of the form –(CH₂)_m-, where m is an integer from 0 to 10. An alkylene chain may be optionally substituted with other functional groups as described herein. [0354] A linker described herein with a maleimide group may include an electron withdrawing group such as, but not limited to, -C(O)R, =O, -CN, -NO₂, -CX3, -X, -COOR, -CONR₂, -COR, -COX, -SO₂R, -SO₂OR, -SO₂NHR, -SO₂NR₂, PO₃R₂, -P(O)(CH3)NHR, -NO, -NR3⁺, -CR=CR2, and -C≡CR, where each R is independently selected from H and C_1-6 alkyl and each X is independently selected from F, Br, Cl, and I. Self-stabilizing linkers may also include aryl, e.g., phenyl, or heteroaryl, e.g., pyridine, groups optionally substituted with electron withdrawing groups such as those described herein. [0355] Examples of self-stabilizing linkers are provided in, e.g., U.S. Patent Publication Number 2013/0309256, the linkers of which are incorporated by reference herein. It will be understood that a self-stabilizing linker useful in conjunction with immune-stimulatory compounds may be equivalently described as unsubstituted maleimide-including linkers, thio-substituted succinimide-including linkers, or hydrolyzed, ring-opened thio-substituted succinimide-including linkers. [0356] In certain embodiments, a linker comprises a stabilizing linker moiety selected from:

. [0357] In the scheme provided above, the bottom structure may be referred to as (maleimido)-DPR-Val-Cit-PAB, where DPR refers to diaminopropinoic acid, Val refers to valine, Cit refers to citrulline, and PAB refers to para-aminobenzylcarbonyl. represents the point of attachment to an immune-stimulatory compound. [0358] A method for bridging a pair of sulfhydryl groups derived from reduction of a native hinge disulfide bond has been disclosed and is depicted in the schematic below. An advantage of this methodology is the ability to synthesize homogenous DAR4 conjugates by full reduction of IgGs (to give 4 pairs of sulfhydryls from interchain disulfides) followed by reaction with 4 equivalents of the alkylating agent. Conjugates containing “bridged disulfides” are also claimed to have increased stability.

[0359] Similarly, as depicted below, a maleimide derivative that is capable of bridging a pair of sulfhydryl groups has been developed.

[0360] A linker can contain the following structural formulas (VIa), (VIb), or (VIc):

or salts thereof, wherein: R^q is H or–O-(CH2CH2O)11-CH3; x is 0 or 1; y is 0 or 1; G² is -CH₂CH₂CH₂SO₃H or–CH₂CH₂O-(CH₂CH₂O)₁₁-CH₃; R^w is–O-CH₂CH₂SO₃H or –NH(CO)-CH2CH2O-(CH2CH2O)12-CH3; and * represents the point of attachment to the remainder of the linker. [0361] Exemplary embodiments of linkers according to structural formula (VIa) and (VIb) that can be included in the conjugates described herein can include the linkers illustrated below (as illustrated, the linkers can include a group suitable for covalently linking the linker to an antibody):

, wherein represents the point of attachment of the linker to an immune-stimulatory compound. [0362] Exemplary embodiments of linkers according to structural formula (VIc) that can be included in the immune-stimulatory conjugates described herein can include the linkers illustrated below (as illustrated, the linkers can include a group suitable for covalently linking the linker to an antibody):

wherein represents the point of attachment of the linker to an immune-stimulatory compound. [0363] A linker can be attached to an antibody at any suitable position. Factors to be considered in selecting an attachment site include whether the linker is cleavable or non-cleavable, the reactive group of the linker for attachment to the antibody, the chemical nature of the immune-stimulatory compound and compatabiltity with reactive sites on the linker and the antibody, and the effect of the attachment site on functional activities of the Fc domain. A linker may be attached to a terminus of an amino acid sequence of an antibody or can be attached to a side chain of an amino acid of an antibody, such as the side chain of a lysine, serine, threonine, cysteine, tyrosine, aspartic acid, glutamine, a non-natural amino acid residue, or glutamic acid residue. A linker may be bound to a terminus of an amino acid sequence of an Fc domain or Fc region of an antibody, or may be bound to a side chain of an amino acid of an Fc domain of an antibody, such as the side chain of a lysine, serine, threonine, cysteine, tyrosine, aspartic acid, glutamine, a non-natural amino acid residue, or glutamic acid residue. [0364] In some embodiments, a linker is attached to a hinge cysteine of an antibody Fc domain. A linker can be attached to an antibody at a light chain constant domain lysine. A linker can be attached to an antibody at an engineered cysteine in the light chain. A linker can be attached to an antibody at an engineered light chain glutamine. A linker can be attached to an antibody at an unnatural amino acid engineered into the light chain. A linker can be attached to an antibody at a heavy chain constant domain lysine. A linker can be attached to an antibody at an engineered cysteine in the heavy chain. A linker can be attached to an antibody at an engineered heavy chain glutamine. A linker can be attached to an antibody at an unnatural amino acid engineered into the heavy chain. Amino acids can be engineered into an amino acid sequence of an antibody as described herein or as known to the skilled artisan and can be connected to a linker of a conjugate. Engineered amino acids can be added to a sequence of existing amino acids. Engineered amino acids can be substituted for one or more existing amino acids of a sequence of amino acids. [0365] A linker can be attached to an antibody via a sulfhydryl group. A linker can be attached to an antibody via a primary amine. A linker can be a link created between an unnatural amino acid on an antibody by reacting with oxime bond that was formed by modifying a ketone group with an alkoxyamine on an immune stimulatory compound. [0366] As is known by skilled artisans, the linker selected for a particular conjugate may be influenced by a variety of factors, including but not limited to, the site of attachment to the antibody (e.g., lys, cys or other amino acid residues), structural constraints of the drug pharmacophore and the lipophilicity of the drug. The specific linker selected for a conjugate should seek to balance these different factors for the specific antibody/drug combination. [0367] For example, conjugates have been observed to effect killing of bystander antigen-negative cells present in the vicinity of the antigen-positive tumor cells. The mechanism of bystander cell killing by conjugates has indicated that metabolic products formed during intracellular processing of the conjugates may play a role. Neutral cytotoxic metabolites generated by metabolism of the conjugates in antigen-positive cells appear to play a role in bystander cell killing while charged metabolites may be prevented from diffusing across the membrane into the medium, or from the medium across the membrane, and therefore cannot affect bystander killing. In certain embodiments, the linker is selected to attenuate the bystander effect caused by cellular metabolites of the conjugate. In certain embodiments, the linker is selected to increase the bystander effect. [0368] The properties of the linker, or linker-compound, may also impact aggregation of the conjugate under conditions of use and/or storage. Typically, conjugates reported in the literature contain no more than 3-4 drug molecules per antibody molecule. Attempts to obtain higher drug-to-antibody ratios (“DAR”) often failed, particularly if both the drug and the linker were hydrophobic, due to aggregation of the conjugate. In many instances, DARs higher than 3-4 could be beneficial as a means of increasing potency. In instances where an immune-stimulatory compound is more hydrophobic in nature, it may be desirable to select linkers that are relatively hydrophilic as a means of reducing conjugate aggregation, especially in instances where DARs greater than 3-4 are desired. Thus, in certain embodiments, a linker incorporates chemical moieties that reduce aggregation of the conjugates during storage and/or use. A linker may incorporate polar or hydrophilic groups such as charged groups or groups that become charged under physiological pH to reduce the aggregation of the conjugates. For example, a linker may incorporate charged groups such as salts or groups that deprotonate, e.g., carboxylates, or protonate, e.g., amines, at physiological pH. [0369] In particular embodiments, the aggregation of the conjugates during storage or use is less than about 40% as determined by size-exclusion chromatography (SEC). In particular embodiments, the aggregation of the conjugates during storage or use is less than 35%, such as less than about 30%, such as less than about 25%, such as less than about 20%, such as less than about 15%, such as less than about 10%, such as less than about 5%, such as less than about 4%, or even less, as determined by size- exclusion chromatography (SEC). Conjugates [0370] A conjugate as described herein comprises an antibody and at least one linker attached to at least one immune-stimulatory compound, such as a myeloid cell agonist or other agonist (e.g., TLR8 agonist, TLR7 agonist, other TLR agonist, STING agonist, RIG-I-Like receptor agonist, C-type lectin receptors agonist, or cytosolic DNA Sensors agonist). In some aspects, the present disclosure provides a conjugate represented by Formula I:

wherein: A is an antibody, L is the linker; Dx is the immune-stimulatory compound; n is selected from 1 to about 20 or 2 to about 10 or 3 to about 8; and z is selected from 1 to 20. [0371] In further aspects, the present disclosure provides an antibody conjugate represented by the formula: wherein: n is selected from 1 to about 20 or 2 to about 10 or 3 to about 8; L³ is a linker; and D is selected from a compound or salt of a compound of any one of Category A Formulas (IA), (IB), (IIA), (IIB), (IIC), (IIIA), (IIIB), (IVA), (IVB), and (IVC), or any one of Category B Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC). [0372] In some embodiments, the immune-stimulatory compound is a myeloid cell agonist. In some embodiments, the immune-stimulatory compound is a TLR8 agonist. In some embodiments, the immune-stimulatory compound is a TLR7 agonist. In some embodiments, the immune-stimulatory compound is a TLR3 agonist. In some embodiments, the immune-stimulatory compound is a TLR4 agonist. In some embodiments, the immune-stimulatory compound is a TLR5 agonist. In some embodiments, the immune-stimulatory compound is a TLR9 agonist. In some embodiments, the immune-stimulatory compound is a STING agonist. In some embodiments, the immune-stimulatory compound is a RIG-I-Like receptor agonist. In some embodiments, the immune-stimulatory compound is a C-type lectin receptors agonist. In some embodiments, the immune-stimulatory compound is a cytosolic DNA Sensors agonist. [0373] In some embodiments, the TLR8 agonist compound is a compound selected from any one of Category A Formulas (IA), (IB), (IIA), (IIB), (IIC), (IIIA), (IIIB), (IVA), (IVB), and (IVC). In some embodiments, TLR7 agonist is a compound selected from any one of Category B Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC). [0374] In some aspects, the present disclosure provides a conjugate comprising at least one immune-stimulatory compound (e.g., a compound or salt thereof), an antibody, and at least one linker, wherein each immune-stimulatory compound is linked, i.e., covalently bound, to the antibody through a linker. The linker can be selected from a cleavable or non-cleavable linker. In some embodiments, the linker is cleavable. In other embodiments, the linker is non-cleavable. Linkers are further described in the present application in the preceeding section, any one of which can be used to connect an antibody to an immune-stimulatory compound. [0375] In a conjugate, the drug loading is represented by z, the number of immune-stimulatory compound-linker molecules per antibody, or the number of immune-stimulatory compounds per antibody, depending on the particular conjugate. Depending on the context, z can represent the average number of immune-stimulatory compound(-linker) molecules per antibody, also referred to the average drug loading. z can range from 1 to 20, from 1-50 or from 1-100. In some conjugates, z is preferably from 1 to 8. In some preferred embodiments, when z represents the average drug loading, z ranges from about 2 to about 5. In some embodiments, z is about 2, about 3, about 4, or about 5. The average number of immune-stimulatory compounds per antibody in a preparation of conjugate may be characterized by conventional means such as mass spectroscopy, liquid chromatography/mass spectrometry (LC/MS), HIC, ELISA assay, and HPLC. [0376] A number of conjugates are consistent with the disclosure herein. The conjugates generally comprise an immune-stimulatory compound covalently bound to an antibody that localizes the conjugate to a target tissue, cell population or cell. The antibody is covalently attached to each immune-stimulatory compound, either directly or through a linker that tethers the immune-stimulatory compound to the antibody. Antibodies listed herein as well as antibodies to antigens or epitiopes thereof listed herein or otherwise known to one of skill in the art are consistent with the conjugates as disclosed herein. [0377] Some exemplary conjugates are as follows. A conjugate can comprise an antibody, at least one immune-stimulatory compound, and optionally at least one linker. A conjugate can comprise an antibody, at least one TLR7 agonist, and at least one linker. A conjugate can comprise an antibody, at least one TLR8 agonist, and at least one linker. A conjugate can comprise an antibody, at least one Compound A TLR8 agonist, and at least one linker. A conjugate can comprise an antibody, at least one Compound B TLR7 agonist, and at least one linker. A conjugate can comprise an antibody, at least one TLR3 agonist, and at least one linker. A conjugate can comprise an antibody, at least one TLR4 agonist, and at least one linker. A conjugate can comprise an antibody, at least one TLR5 agonist, and at least one linker. A conjugate can comprise an antibody, at least one TLR9 agonist, and at least one linker. A conjugate can comprise an antibody, at least one STING agonist, and at least one linker. A conjugate can comprise an antibody, at least one RIG-I agonist, and at least one linker. A conjugate can comprise an antibody, at least one C-type lectin receptor agonist, and at least one linker. A conjugate can comprise an antibody, at least one cytosolic DNA Sensors agonist, and at least one linker. [0378] In some embodiments, the immune stimulatory compound is a myeloid cell agonist. A number of myeloid cell agonists are consistent with the disclosure herein such as a TLR8 agonist. Exemplary TLR8 agonists are provided herein. In some embodiments, a myeloid cell agonist-linker compound (Linker-Payload) is selected from any of Linker-Payloads provided herein. Category A and Category B Conjugates [0379] In certain embodiments, the disclosure provides an immune-stimulatory conjugate (or conjugate) of a or an antibody and at least one compound of any one of Category A Formulas (IA), (IB), (IIA), (IIB), (IIC), (IIIA), (IIIB), (IVA), (IVB), and (IVC), each compound optionally attached to the antibody via a linker. In certain embodiments, the disclosure provides an immune-stimulatory conjugate of an antibody and at least one compound of any one of Category B Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), each compound optionally attached to the antibody via a linker. In certain embodiments, the average Drug-to-Antibody Ratio (DAR) of the pharmaceutical composition is selected from 1 to about 8, 2 to about 6, about 3 to about 5, or about 4. [0380] In certain embodiments, the disclosure provides a pharmaceutical composition suitable for intravenous or subcutaneous administration, comprising an immune stimulatory conjugate of a compound of any one of Category A Formulas (IA), (IB), (IIA), (IIB), (IIC), (IIIA), (IIIB), (IVA), (IVB), and (IVC) and a pharmaceutically acceptable excipient. In certain embodiments, the disclosure provides a pharmaceutical composition suitable for intravenous or subcutaneous administration, comprising an immune stimulatory conjugate of a compound of any one of Category B Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), and a pharmaceutically acceptable excipient. In certain embodiments, the average Drug-to-Antibody Ratio (DAR) of the pharmaceutical composition is selected from 1 to about 8, 2 to about 6, about 3 to about 5, or about 4. [0381] In certain embodiments, the disclosure provides a method for the treatment of a disease treatable by a TLR agonist (e.g., cancer, viral disease) comprising subcutaneously administering an effective amount of a conjugate of a compound of any one of Category A Formulas (IA), (IB), (IIA), (IIB), (IIC), (IIIA), (IIIB), (IVA), (IVB), and (IVC), or a pharmaceutical composition thereof suitable for intravenous or subcutaneous administration to a subject in need thereof. In certain embodiments, the disclosure provides a method for the treatment of cancer (e.g., breast, lung, stomach/gastric, colorectal) or viral infection (e.g., HBV, HCV), comprising intravenously or subcutaneously administering an effective amount of the conjugate of a compound of any one of Category B Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), or a pharmaceutical composition thereof suitable for subcutaneous administration to a subject in need thereof. In any of the embodiments herein, the conjugate may be administered by slow infusion. [0382] The disclosure provides a method of preparing an antibody conjugate of the formula:

wherein: n is selected from 1 to 20; L³ is a linker; and D is selected from a compound or salt of a compound of any one of Category A Formulas (IA), (IB), (IIA), (IIB), (IIC), (IIIA), (IIIB), (IVA), (IVB), and (IVC), and Category B Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), comprising contacting D-L³ with an antibody. [0383] The disclosure provides a method of preparing an antibody conjugate of the formula:

wherein: n is selected from 1 to 20; L³ is a linker; and D is selected from a compound of any one of Category A Formulas (IA), (IB), (IIA), (IIB), (IIC), (IIIA), (IIIB), (IVA), (IVB), and (IVC), and Category B Formulas (IA), (IB), (IC), (IIA), (IIB), and (IIC), comprising contacting L³ with the antibody to form L³-antibody and contacting L³ antibody with D to form the conjugate. [0384] In some embodiments, L³ and D together have a structure selected from:

,

,

,

, and a salt of any one thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody. [0385] In some embodiments, RX^* comprises a succinamide moiety and is bound to a cysteine residue of an antibody. In some embodiments, RX^* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of an antibody. [0386] The compounds disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of ²H, ³H, ¹¹C, ¹³C and/or ¹⁴C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos.5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy, thus increasing the duration of action of drugs. [0387] Unless otherwise stated, structures depicted herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by ¹³C- or ¹⁴C-enriched carbon are within the scope of the present disclosure. [0388] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more atoms that constitute such compounds. For example, the compounds may be labeled with isotopes, such as for example, deuterium (²H), tritium (³H), iodine-125 (¹²⁵I) or carbon-14 (¹⁴C). Isotopic substitution with ²H, ¹¹C, ¹³C, ¹⁴C, ¹⁵C, ¹²N, ¹³N, ¹⁵N, ¹⁶N, ¹⁶O, ¹⁷O, ¹⁴F, ¹⁵F, ¹⁶F, ¹⁷F, ¹⁸F, ³³S, ³⁴S, ³⁵S, ³⁶S, ³⁵Cl, ³⁷Cl, ⁷⁹Br, ⁸¹Br, ¹²⁵I are all contemplated. All isotopic variations of the compounds of the present disclosure, whether radioactive or not, are encompassed within the scope of the present disclosure. [0389] In certain embodiments, the compounds disclosed herein have some or all of the ¹H atoms replaced with ²H atoms. The methods of synthesis for deuterium- containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods. [0390] Deuterium substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32. [0391] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide for the synthesis of deuterium- containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co. [0392] Compounds of the present disclosure also include crystalline and amorphous forms of those compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof. [0393] Included in the present disclosure are salts, particularly pharmaceutically acceptable salts, of the compounds described herein. The compounds of the present disclosure that possess a sufficiently acidic, a sufficiently basic, or both functional groups, can react with any of a number of inorganic bases, and inorganic and organic acids, to form a salt. Alternatively, compounds that are inherently charged, such as those with a quaternary nitrogen, can form a salt with an appropriate counterion, e.g., a halide such as bromide, chloride, or fluoride. [0394] The compounds described herein may in some cases exist as diastereomers, enantiomers, or other stereoisomeric forms. The compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms as well as the appropriate mixtures thereof. Separation of stereoisomers may be performed by chromatography or by forming diastereomers and separating by recrystallization, or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions,” John Wiley and Sons, Inc., 1981, herein incorporated by reference for this disclosure). Stereoisomers may also be obtained by stereoselective synthesis. [0395] The methods and compositions described herein include the use of amorphous forms as well as crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. As well, active metabolites of these compounds having the same type of activity are included in the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. The solvated forms of the compounds presented herein are also considered to be disclosed herein. [0396] In certain embodiments, compounds or salts of the compounds described herein may be prodrugs attached to antibodies to form conjugates. The term “prodrug” is intended to encompass compounds which, under physiologic conditions, are converted into active compounds, e.g., TLR8 agonists, TLR7 agonists, other TLR agonists, STING agonist, RIG-I-Like receptor agonists, C-type lectin receptors agonists, or cytosolic DNA Sensors agonists. One method for making a prodrug is to include one or more selected moieties which are hydrolyzed or otherwise cleaved under physiologic conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the host animal such as specific target cells in the host animal. [0397] Prodrug forms of the herein described compounds, wherein the prodrug is metabolized in vivo to produce a compound described herein are included within the scope of the claims. In some cases, some of the herein-described compounds may be a prodrug for another derivative or active compound. [0398] In certain embodiments, an immune-stimulatory compound, such as a TLR8 agonist or TLR7 agonist, is modified as a prodrug with a masking group, such that the TLR8 agonist, TLR7 agonist or other agonist, has limited activity or is inactive until it reaches an environment where the masking group is removed to reveal the active compound. For example, a TLR8 agonist or TLR7 agonist can be covalently modified at an amine involved in binding to the active site of a TLR8 receptor such that the compound is unable to bind the active site of the receptor in its modified (prodrug) form. In such an example, the masking group is removed under physiological conditions, e.g., enzymatic or acidic conditions, specific to the site of delivery, e.g., intracellular or extracellular adjacent to target cells. Masking groups may be removed from the amine of the compound or salt described herein due to the action of lysosomal proteases, e.g., cathepsin and plasmin. These proteases can be present at elevated levels in certain tumor tissues. The masking group may be removed by a lysosomal enzyme. The lysosomal enzyme can be, for example, cathepsin B, cathepsin S, β-glucuronidase, or β-galactosidase. [0399] In certain embodiments, an amine masking group inhibits binding of the amine group of the compound with residues of a TLR8 receptor. The amine masking group may be removable under physiological conditions within a cell but remains covalently bound to the amine outside of a cell. Masking groups that may be used to inhibit or attenuate binding of an amine group of a compound with residues of a TLR8 receptor include, for example, peptides and carbamates. [0400] Synthetic chemistry transformations and methodologies useful in synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser’s Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995). [0401] The activation, stimulation or augmentation of an immune response by an immune-stimulatory conjugate, such as a myeloid cell agonist, can be measured in vitro by co-culturing immune cells (e.g., myeloid cells) with cells targeted by the conjugate and measuring cytokine release, chemokine release, proliferation of immune cells, upregulation of immune cell activation markers, ADCC, or any combination thereof. ADCC can be measured by determining the percentage of remaining target cells in the co-culture after administration of the conjugate with the target cells, myeloid cells, and other immune cells. In some embodiments, an immune-stimulatory conjugate can activate or stimulate immune cell activity, as determined by in vitro assay, such as a cytokine release assay, by detection of activation markers (e.g., MHC class II markers) or other assays known in the art. In some embodiments, an immune-stimulatory conjugate has an EC50 of 100 nM or less, as determine by cytokine release assay. In some embodiments, an immune-stimulatory conjugate has an EC50 of 50 nM or less, as determine by cytokine release assay. In some embodiments, an immune-stimulatory conjugate has an EC50 of 10 nM or less, as determine by cytokine release assay. In some embodiments, an immune-stimulatory conjugate has an EC50 of 1mM or less. Exemplary Combination Therapy [0402] Conjugates described herein can be administered in combination with one or more other modes of treatment in a combination therapy. The other mode or modes of treatment can be provided before, substantially contemporaneous with, and/or after the immune-stimulatory conjugate. Exemplary combination therapies comprise an immune-stimulatory conjugate described herein and a second anti-cancer agent. In some embodiments, the second anti-cancer agent is a small molecule chemotherapy and/or a biologic therapy, such as a therapeutic antibody. In some embodiments, the second anti-cancer agent is or comprises an immune checkpoint inhibitor, a therapeutic comprising a HER2-targeting agent, a kinase inhibitor, or a molecularly targeted therapy. In some embodiments, a combination therapy comprises surgery and/or radiation therapy in addition to an immune-stimulatory conjugate described herein, with or without a second anti-cancer agent. [0403] Second anti-cancer agents useful in the methods provided herein include, for example, chemotherapy agents, ionizing radiation, chemotherapy protective agents, molecularly targeted therapy, anti-cancer biologic therapy, immune checkpoint inhibitor, therapeutic agents targeting HER2, kinase inhibitors, and other anti-cancer drugs. Examples of chemotherapy agents contemplated as further therapeutic agents include alkylating agents, such as nitrogen mustards (e.g., mechlorethamine, cyclophosphamide, ifosfamide (IFEX®), melphalan (Alkeran®), and chlorambucil); bifunctional chemotherapeutics (e.g., bendamustine); nitrosoureas (e.g., carmustine (BCNU, BiCNU®; polifeprosan 20 implant (Gliadel®)), lomustine (CCNU), and semustine (methyl-CCNU)); ethyleneimines and methyl-melamines (e.g., triethylenemelamine (TEM), triethylene thiophosphoramide (thiotepa), and hexamethylmelamine (HMM, altretamine)); alkyl sulfonates (e.g., busulfan (Myleran®), busulfan injection (Busulfex®)); and triazines (e.g., dacabazine (DTIC)); antimetabolites, such as folic acid analogues (e.g., methotrexate (Folex®), trimetrexate, and pemetrexed (multi-targeted antifolate)); pyrimidine analogues (such as 5- fluorouracil (5-FU, Adrucil®, Efudex®), capecitabine (Xeloda®), fluorodeoxyuridine, tezacitabine, gemcitabine, cytosine arabinoside (AraC, cytarabine (Cytosar-U®); cytarabine liposome injection (DepoCyt®)), 5-azacytidine, and 2,2ʹ- difluorodeoxycytidine); purine analogues (e.g., 6-mercaptopurine (Purinethol®), 6- thioguanine, azathioprine, 2ʹ-deoxycoformycin (pentostatin), erythrohydroxynonyladenine (EHNA), fludarabine phosphate (Fludara®), 2 chlorodeoxyadenosine (cladribine, 2-CdA)); Type I topoisomerase inhibitors such as camptothecin (CPT), topotecan (Hycamptin®), and irinotecan (Camptosar®); natural products, such as epipodophylotoxins (e.g., etoposide (Vepesid®) and teniposide (Vumon®)); vinca alkaloids (e.g., vinblastine (Velban®), vincristine (Oncovin®), and vinorelbine (Navelbine®)); anti-tumor antibiotics such as actinomycin D (dactinomycin, Cosmegan®), doxorubicin hydrochloride (Adriamycin®, Rubex®), mitoxantrone (Novantrone®), and bleomycin sulfate (Blenoxane®); radiosensitizers such as 5-bromodeozyuridine, 5-iododeoxyuridine, and bromodeoxycytidine; platinum coordination complexes such as cisplatin (Platinol®), carboplatin (Paraplatin®), and oxaliplatin (Eloxatin®); substituted ureas, such as hydroxyurea (Hydrea®); microtubule inhibitors such as paclitaxel (Taxol®), docetaxel (Taxotere®), and eribulin (Halaven®); FOLFOX (a chemotherapy regimen comprising Folinic acid (leucovorin) "FOL", Fluorouracil (5-FU) "F", and Oxaliplatin (Eloxatin) "OX"); immunosuppressive agents such as cyclophosphamide (Cytoxan® or Neosar®); hormone-based compound such as anastrozole (Arimidex®), exemestane (Aromasin®), letrozole (Femara®), fulvestrant (Faslodex®), bicalutamide (Casodex®), Flutamide (Eulexin®), Nilutamide (Nilandron®), Enzalutamide (Xtandi®), apalutamide (Erleada®), darolutamide (Nubeqa®), Degarelix (Firmagon®), Toremifene (Fareston®), goserelin (Zoladex®), Triptorelin (Trelstar®), Histrelin (Vantas®), leuprolide (Lupron®) and tamoxifen citrate (Nolvadex®); an anti-inflammatory agent such as dexamethasone; an anti- androgen compound such as flutamide (Eulexin®); an anthracycline compound such as idarubicin (Idamycin®, Zavedos®) and epirubicin (Ellence®); bioreductive anti-cancer agent such as tirapazamine (Tirazone®); serine/threonine kinase inhibitors such as CDK4/6 inhibitors abemaciclib (Verzenio®), palbociclib (Ibrance®), and ribociclib (Kisqali®); tyrosine kinase inhibitors such as tucatinib, cabozantinib, afatinib, erlotinib, pyrotinib, neratinib, poziotinib, dacomitinib, gefitinib, lapatinib, osimertinib, larotrectinib, axitinib, lenvatinib, pazopanib, regorafenib, and sunitinib; and methylhydrazine derivatives such as N methylhydrazine (MIH) and procarbazine. [0404] Anticancer molecularly targeted therapy target specific molecules involved in the development, growth and spread of cancer cells. In some embodiments, a molecularly targeted therapy is a small molecule or comprises an antibody or antigen binding fragment. Examples of molecularly targeted include ALK inhibitors such as crizotinib, ceritinib, and alectinib; BCL2 inhibitors such as venetoclax, obatoclax, navitoclax, and gossypol; PARP inhibitors such as iniparib and olaparib; BRAF inhibitors such as vemurafenib and dabrafenib; and angiogenesis inhibitors such as VEGF and/or VEGFR inhibitors, including axitinib, sunitinib, pazopanib, cabozantinib, vandetanib, motesanib, regorafenib, cediranib, lenvatinib, sorafenib, ziv-aflibercept, aflibercept, ranibizumab, ramucirumab, and bevacizumab. [0405] Examples of anti-cancer biologic therapy include biologic therapy comprising antibodies (e.g., therapeutic antibodies or antigen binding fragments thereof, antibody conjugates, cellular immunotherapy (e.g., chimeric antigen receptor (CAR) T cells, T cell receptor (TCR) immunotherapy, dendritic cell therapy), and Fc- fusion proteins. In some embodiments, an anti-cancer biologic therapy targets a tumor antigen, or a molecule in involved in development, growth, and/or spread of cancer cells (molecularly targeted immunotherapy). Examples of antibody conjugate therapy contemplated for use as therapeutic agents include, for example, sacituzumab govitecan and enfortumab vedotin. [0406] In some embodiments, additional anti-cancer agents useful in the methods provided herein include chemotherapy protective agents that prevent or descrease toxic side effects of chemotherapy agents. Examples of chemotherapy protect agents contemplated for use as further therapeutic agents include, for example, leucovorin (folinic acid), allpuronol (Zyloprim®), rasburicase (Fasturtec®), amifostine (Ethyol®), dexrazoxane (Zinecard®), and mesna (Mesnex®). [0407] In certain embodiments, the combination therapy comprises a conjugate described herein and palbociclib. In further embodiments, the combination therapy comprises a conjugate described herein and abemaciclib. In still further embodiments, the combination therapy comprises a conjugate described herein and ribociclib. Immune Checkpoint Inhibitors [0408] In some embodiments, combination therapies comprise a conjugate described herein and a second anti-cancer agent, wherein the second anti-cancer agent is or comprises an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor is an antagonist of PD-1, PD-L1, and/or PD-L2. In some embodiments, the antagonist of PD-1, PD-L1, and/or PD-L2 is a small molecule, such as INCB 86550, 1,3,4- and 1,2,4-oxadiazole and 1,3,4- and 1,2,4-thiadiazole compounds (see WO 2015/033301 WO 2016/142894; WO 2016/142833, WO 2018/051255; WO 2018/07375, and Guzik et al., Molecules 24:2071, 2019, the compounds from which are incorporated herein by reference), and GS-4224; peptides and peptidomimetics such as AUNP-12 and heptapeptide SNTSEFS-NH2 (SEQ ID NO: 12)); macrocyclic peptides such as BMS-57, BMS-71, and BMS99; ansamycin class of antibiotics such as geldanamycin and rifabutin; Fc-fusion proteins, such as AMP-224; and antibodies, such as pembrolizumab (KEYTRUDA^®); pembrolizumab biosimilar; nivolumab (OPDIVO^®); nivolumab biosimilar; pidilizumab; pidilizumab biosimilar; cemiplimab; AMP-514 (MEDI0608, see U.S. Patent No.8,609,089,B2); MDX-1105; dostarlimab; tislelizumab; KD-033, AGEN2034; STI-A1010; STI-A1110; durvalumab; atezolizumab; avelumab; BMS-936559; or a PD-1 antibody disclosed in U.S. Patent No.8,008,449; 6,808,710; 7,488,802; 8,168,75; or 8,354,509; or PCT Publication No. WO 2012/145493. In some embodiments, the immune checkpoint inhibitor is an anti- PD1 antibody selected from pembrolizumab (KEYTRUDA®); pembrolizumab biosimilar; nivolumab (OPDIVO®); nivolumab biosimilar; pidilizumab; pidilizumab biosimilar; toripalimab; cemiplimab; cemiplimab biosimilar; dostarlimab; tislelizumab; BMS-936559; AMP-514 (MEDI0608, see U.S. Patent No.8,609,089,B2); AGEN2034; and STI-A1110. In some embodiments, the immune checkpoint inhibitor is an anti-PD- L1 antibody selected from atezolizumab; atezolizumab biosimilar; durvalumab; durvalumab biosimilar; avelumab; avelumab biosimilar; MDX-1105; BMS-936559; KD-033; and STI-A1010. [0409] In certain embodiments, the immune checkpoint inhibitor is an inhibitor of TIGIT, e.g., an anti-TIGIT antibody such as tiragolumab. [0410] In some embodiments, the combination therapy comprises a conjugate described herein and an additional therapeutic agent comprising pembrolizumab, nivolumab, pidilizumab, or a biosimilar thereof. In certain embodiments, the combination therapy comprises a conjugate described herein and pembrolizumab or a biosimilar thereof. In certain further embodiments, the combination therapy comprises a conjugate described herein and nivolumab or a biosimilar thereof. Therapeutic Agents Targeting HER2 [0411] In some embodiments, combination therapies comprise a conjugate described herein and an additional therapeutic agent targeting HER2, such as kinase inhibitors and/or therapeutic agents comprising an anti-HER2 antibody. In some embodiments, a kinase inhibitor is a tyrosine kinase inhibitor or a serine/threonine kinase inhibitor, including a CDK4/6 inhibitor. In some embodiments, a CDK4/6 inhibitor is selected from abemaciclib (Verzenio®), palbociclib (Ibrance®), and ribociclib (Kisqali®). Nonlimiting exemplary tyrosine kinase inhibitors include tucatinib, cabozantinib, afatinib, erlotinib, pyrotinib, neratinib, poziotinib, dacomitinib, gefitinib, lapatinib, osimertinib, larotrectinib, axitinib, lenvatinib, pazopanib, regorafenib, and sunitinib. In some embodiments, the tyrosine kinase inhibitor is selected from tucatinib, cabozantinib, pyrotinib, neratinib, and poziotinib. In some embodiments, an additional therapeutic is an adenosine receptor antagonist, such as AB928. Therapeutic agents comprising an anti-HER2 antibody include anti-HER2 antibodies or antigen binding fragments thereof and anti-HER2 antibody conjugates. In some embodiments, the therapeutic agent comprising an anti-HER2 antibody is selected from trastuzumab, a trastuzumab biosimilar (such as trastuzumab-qyyp (TRAZIMERA™), trastuzumab-pkrb (HERZUMA®), trastuzumab-dttb (ONTRUZANT®), trastuzumab-anns (KANJINTI™), trastuzumab-dkst (Ogivri™), fam-trastuzumab deruxtecan-nxki (ENHERTU®, DS-8201), ado-trastuzumab emtansine (KADCYLA®), trastuzumab duocarmazine (SYD985), PF-06804103, trastuzumab auristatin-0101, margetuximab, zenocutuzumab (MCLA-128), ZW25 (Zymeworks); ZW49 (Zymeworks); RC48-ADC (RemeGen); RG6148 (DHES0815A); or RG6194 (BTRC4017A). [0412] In some embodiments, the combination therapy comprises a conjugate described herein and an additional therapeutic agent selected from any one of trastuzumab, trastuzumab-qyyp, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-anns, trastuzumab-dkst, and margetuximab. In certain embodiments, the combination therapy comprises a conjugate described herein and trastuzumab. In certain further embodiments, the combination therapy comprises a conjugate described herein and trastuzumab-qyyp. [0413] In further embodiments, the combination therapy comprises a conjugate described herein and an additional therapeutic agent selected from any one of fam- trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, and trastuzumab duocarmazine. In certain embodiments, the combination therapy comprises a conjugate described herein and fam-trastuzumab deruxtecan-nxki. In certain embodiments, the combination therapy comprises a conjugate described herein and ado-trastuzumab emtansine. [0414] In some embodiments, the combination therapy comprises a conjugate described herein and an additional therapeutic agent selected from any one of tucatinib, pyrotinib, neratinib, and poziotinib. In certain embodiments, the combination therapy comprises a conjugate described herein and tucatinib. Pharmaceutical Formulations [0415] The conjugates described herein are useful as pharmaceutical compositions for administration to a subject in need thereof. Pharmaceutical compositions can comprise the conjugates described herein and one or more pharmaceutically acceptable excipients, suitable for administration by a selected route. A pharmaceutical composition can comprise any conjugate described herein. A pharmaceutical composition can further comprise buffers, carbohydrates, and/or preservatives, as appropriate. Pharmaceutical compositions comprising a conjugate can be manufactured, for example, by lyophilizing the conjugate, mixing, dissolving, emulsifying, encapsulating or entrapping the conjugate. The pharmaceutical compositions can also include the conjugates described herein in a free-base form or pharmaceutically-acceptable salt form. [0416] Methods for formulation of the pharmaceutical compositions can include formulating any of the conjugates described herein with one or more inert, pharmaceutically-acceptable excipients or carriers to form a solid, semi-solid, or liquid composition for intravenous or subcutaneous administration. Solid compositions can include, for example, powders, and in some aspects, the solid compositions further contain nontoxic, auxiliary substances, for example wetting or emulsifying agents, pH buffering agents, and other pharmaceutically-acceptable additives. Alternatively, the compositions described herein can be lyophilized or in powder form for re-constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use [0417] The pharmaceutical compositions and formulations can be sterilized. Sterilization can be accomplished by filtration through sterile filtration. [0418] The pharmaceutical compositions described herein can be formulated for administration as an injection, e.g., an intravenous or subcutaneous injection. Non- limiting examples of formulations for injection can include a sterile suspension, solution or emulsion in oily or aqueous vehicles. Suitable oily vehicles can include, but are not limited to, lipophilic solvents or vehicles such as fatty oils or synthetic fatty acid esters, or liposomes. Aqueous injection suspensions can contain substances which increase the viscosity of the suspension. The suspension can also contain suitable stabilizers. Alternatively, the pharmaceutical compositions described herein can be lyophilized or in powder form for reconstitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. [0419] The conjugates can be formulated for administration in a unit dosage form in association with a pharmaceutically acceptable vehicle. Such vehicles can be inherently nontoxic, and non-therapeutic. A vehicle can be water, saline, Ringer’s solution, dextrose solution, and 5% human serum albumin. Nonaqueous vehicles such as fixed oils and ethyl oleate can also be used. The vehicle can contain minor amounts of additives such as substances that enhance isotonicity and chemical stability (e.g., buffers and preservatives). [0420] In some embodiments, an aqueous formulation of a conjugate provided herein, such as for subcutaneous administration, has a pH from 4-5.2. The aqueous formulation may comprise one or more excipients, such as, for example, one or more buffering agents, one or more lyoprotectants, and the like. In some embodiments, the pH of the formulation is from 4-5.1, 4.1-5.1, 4.2-5.1, 4.3-5.1, 4.4-5.1, 4.5-5.1, 4-5, 4.1- 5, 4.2-5, 4.3-5, 4.4-5, or 4.5-5. In some embodiments, the formulation comprises at least one buffer. In various embodiments, the buffer may be selected from histidine, citrate, aspartate, acetate, phosphate, lactate, tromethamine, gluconate, glutamate, tartrate, succinate, malic acid, fumarate, α-ketoglutarate, and combinations thereof. In some embodiments, the buffer is at least one buffer selected from histidine, citrate, aspartate, acetate, and combinations thereof. In some embodiments, the buffer is a combination of histidine and aspartate. In some embodiments, the total concentration of the buffer in the aqueous formulation is 10mM to 40mM, such as 15mM-30mM, 15mM-25mM, or 20 mM. [0421] In some embodiments, the aqueous formulation comprises at least one lyoprotectant. In some such embodiments, the at least one lyoprotectant is selected from sucrose, arginine, glycine, sorbitol, glycerol, trehalose, dextrose, alpha- cyclodextrin, hydroxypropyl beta-cyclodextrin, hydroxypropyl gamma-cyclodextrin, proline, methionine, albumin, mannitol, maltose, dextran, and combinations thereof. In some embodiments, the lyoprotectant is sucrose. In some embodiments, the total concentration of lyoprotectant in the aqueous formulation is 3-12%, such as 5-12%, 6- 10%, 5-9%, 7-9%, or 8%. [0422] In some embodiments, the aqueous formulation comprises at least one surfactant. Exemplary surfactants include polysorbate 80, polysorbate 20, poloxamer 88, and combinations thereof. In some embodiments, the aqueous formulation comprises polysorbate 80. In some embodiments, the total concentration of the at least one surfactant is 0.01%-0.1%, such as 0.01%-0.05%, 0.01%-0.08%, or 0.01%-0.06%, 0.01%-0.04%, 0.01%-0.03%, or 0.02%. [0423] In some embodiments, the concentration of the conjugate in the aqueous formulation is 1 mg/mL-200 mg/mL, such as 10 mg/mL-160 mg/mL, 10 mg/mL-140 mg/mL, 10 mg/mL-120 mg/mL, 20 mg/mL-120 mg/mL, or 30 mg/mL-120 mg/mL, or 40 mg/mL-120 mg/mL, or 40 mg/mL-100 mg/mL. In some embodiments, the concentration of the conjugate in the aqueous formulation is 10 mg/mL-140 mg/mL or 40 mg/mL-140 mg/mL. Therapeutic Applications [0424] The combination therapies provided herein are useful for treating plurality of different subjects including, but not limited to, a mammal, human, non- human mammal, a domesticated animal (e.g., laboratory animals, household pets, or livestock), non-domesticated animal (e.g., wildlife), dog, cat, rodent, mouse, hamster, cow, bird, chicken, fish, pig, horse, goat, sheep, rabbit, and any combination thereof. In various embodiments, the subject is a human. [0425] In various embodiments, methods of treating cancer (e.g., breast, lung, stomach/gastric, colorectal) or viral infection (e.g., HBV, HCV) are provided, comprising administering to a subject with cancer or viral infection an immune checkpoint inhibitor and a conjugate provided herein, wherein the conjugate comprises an antibody that binds a tumor associated antigen for cancer, or a liver cell antigen for viral infection. In some such embodiments, the immune checkpoint inhibitor is an antibody. In some such embodiments, the immune checkpoint inhibitor is an inhibitor of PD-1 and/or PD-L1, e.g., an anti-PD-1 and/or anti-PD-L1 antibody. In certain embodiments, the immune checkpoint inhibitor is an inhibitor of TIGIT, e.g., an anti- TIGIT antibody such as tiragolumab. [0426] Nonlimiting exemplary inhibitors of PD-1 and/or PD-L1 include pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, and durvalumab, or a biosimilar thereof. In some embodiments, the immune checkpoint inhibitor is an anti- PD1 antibody selected from pembrolizumab, nivolumab, zimberelimab, and cemiplimab, or a biosimilar thereof. In some embodiments, the immune checkpoint inhibitor is an anti-PD-L1 antibody selected from atezolizumab, avelumab, and durvalumab, or a biosimilar thereof. [0427] In some embodiments, the conjugate comprises an antibody that binds HER2. In some embodiments, the anti-HER2 antibody of the conjugate comprises the CDRs of pertuzumab, antigen binding fragment (e.g., variable regions) of pertuzumab, light and heavy chains of pertuzumab. In some embodiments, the anti-HER2 antibody of the conjugate comprises the CDRs of trastuzumab, antigen binding fragment (e.g., variable regions) of trastuzumab, light and heavy chains of trastuzumab. [0428] In some such embodiments, the anti-HER2 antibody of the conjugate comprises heavy chain (HC)-CDR1, HC-CDR2, HC-CDR3, light chain (LC)-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively. In further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain and light chain, wherein: (a) the heavy chain comprises HC-CDR1, HC-CDR2, and HC-CDR3 of SEQ ID NOs: 1-3, respectively, and comprises a heavy chain variable region (V_H) having an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the VH amino acid sequence of SEQ ID NO: 7; and (b) the light chain comprises LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 4-6, respectively, and a light chain variable region (VL) having an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the V_L amino acid sequence of SEQ ID NO: 8. In still further embodiments, the anti- HER2 antibody of the conjugate comprises a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 7 and a V_L comprising or consisting of the amino acid sequence of SEQ ID NO: 8. In yet further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain and light chain, wherein: (a) the heavy chain comprises HC-CDR1, HC-CDR2, and HC-CDR3 of SEQ ID NOs: 1-3, respectively, and comprises an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the heavy chain amino acid sequence of SEQ ID NO: 9; and (b) the light chain comprises LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 4-6, respectively, and an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the light chain amino acid sequence of SEQ ID NO: 10. In yet further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain comprising or consisting of the amino acid sequence of SEQ ID NO: 9 and a light chain comprising or consisting of the amino acid sequence of SEQ ID NO: 10. [0429] In some such embodiments, the method comprises administering an additional therapeutic agent. In some such embodiments, the additional therapeutic agent comprises a chemotherapy agent, a kinase inhibitor, a therapeutic agent targeting HER2, a biologic therapy such as a therapeutic antibody, a molecularly targeted therapy, a chemotherapy protective agent, or any combination thereof. [0430] In some such embodiments, the therapeutic agent is a therapeutic agent targeting HER-2, such as kinase inhibitors and/or therapeutic agents comprising an anti- HER2 antibody. In some such embodiments, the therapeutic agent targeting HER2 is selected from trastuzumab, trastuzumab-qyyp, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-anns, trastuzumab-dkst, trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, trastuzumab, duocarmazine, margetuximab, zenocutuzumab (MCLA-128), tucatinib, cabozantinib, pyrotinib, neratinib, and poziotinib. In some such embodiments, the therapeutic agent targeting HER2 comprises an anti-HER2 antibody, e.g., an anti-HER2 antibody or antigen binding fragment thereof, or anti-HER2 antibody conjugate. In some such embodiments, the therapeutic agent comprising an anti-HER2 antibody is selected from trastuzumab, trastuzumab-qyyp, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-anns, trastuzumab-dkst, trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, trastuzumab, duocarmazine, margetuximab, zenocutuzumab (MCLA-128). [0431] In some such embodiments, the kinase inhibitor is a tyrosine kinase inhibitor or a serine/threonine kinase inhibitor, such as a CDK4/6 inhibitor. In some embodiments, a tyrosine kinase inhibitor is tucatinib, cabozantinib, afatinib, erlotinib, pyrotinib, neratinib, poziotinib, dacomitinib, gefitinib, lapatinib, osimertinib, larotrectinib, axitinib, lenvatinib, pazopanib, regorafenib, or sunitinib. In some embodiments, the tyrosine kinase inhibitor is tucatinib, cabozantinib, pyrotinib, neratinib, or poziotinib. In some embodiments the CDK4/6 inhibitor is abemaciclib, palbociclib, or ribociclib. [0432] In some such embodiments, the chemotherapy agent comprises a hormone-based compound, optionally wherein the hormone based compound comprises anastrozole, exemestane, letrozole, fulvestrant, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide, degarelix, toremifene, goserelin, triptorelin, histrelin, leuprolide, or tamoxifen citrate. [0433] In some such embodiments, the chemotherapy agent comprises a platinum coordination complex, optionally wherein the platinum coordination complex comprises cisplatin, oxaliplatin, or carboplatin. [0434] In some such embodiments, the chemotherapy agent comprises a folic acid analog, optionally wherein the folic acid analog comprises pemetrexed, methotrexate, or trimetrexate. [0435] In some such embodiments, the chemotherapy agent comprises a pyrimidine analog, optionally wherein the pyrimidine analog comprises fluorouracil, capecitabine, fluorodeoxyuridine, tezacitabine, gemcitabine, cytosine arabinoside, cytarabine, 5-azacytidine, or 2,2ʹ-difluorodeoxycytidine. [0436] In some such embodiments, the chemotherapy agent comprises a microtubule inhibitor, optionally wherein the microtubule inhibitor comprises paclitaxel, docetaxel, and eribulin. [0437] In some such embodiments, the chemotherapy protective agent comprises leucovorin (folinic acid), allpuronol, rasburicase, amifostine, dexrazoxane, or mesna. [0438] In any of the aforementioned embodiments, the linker-payload compound of the conjugate has a structure selected from:

and a salt of any one thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein

on RX* represents the point of attachment to the residue of the antibody. In some embodiments, RX^* comprises a succinamide moiety and is bound to a cysteine residue of an antibody. In some embodiments, RX^* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of an antibody. [0439] In certain embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

wherein: A is an antibody; n is one; z is selected from 2 to about 8 or from 2 to about 4; L is the linker; and Dx is the immune-stimulatory compound; wherein: L and D_x have a structure of:

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; and (b) pembrolizumab. [0440] In certain embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) fam-trastuzumab deruxtecan-nxki. [0441] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) ado-trastuzumab emtansine. [0442] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) a chemotherapy agent comprising pemetrexed; and (d) a chemotherapy agent comprising carboplatin; and optionally wherein the cancer is a non-small cell lung cancer (NSCLC). [0443] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

wherein: A is an antibody; n is one; z is selected from 2 to about 8 or from 2 to about 4; L is the linker; and D_x is the immune-stimulatory compound; wherein: L and Dx have a structure of:

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) a chemotherapy agent comprising pemetrexed; and (d) a chemotherapy agent comprising cisplatin; and optionally wherein the cancer is a NSCLC. [0444] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) atezolizumab; (c) bevacizumab; (d) a chemotherapy agent comprising carboplatin; and (e) a chemotherapy agent comprising paclitaxel; and optionally wherein the cancer is a NSCLC. [0445] In certain embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; and (b) nivolumab. [0446] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) trastuzumab. [0447] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) fam-trastuzumab deruxtecan-nxki. [0448] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) ado-trastuzumab emtansine. [0449] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) tucatinib. [0450] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

wherein: A is an antibody; n is one; z is selected from 2 to about 8 or from 2 to about 4; L is the linker; and D_x is the immune-stimulatory compound; wherein: L and D_x have a structure of:

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) palbociclib. [0451] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) abemaciclib. [0452] In certain embodiments, a method of treating HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) ribociclib. [0453] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2antigen; (b) trastuzumab; and (c) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0454] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0455] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0456] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0457] In further embodiments, a method of treating HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; and (c) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0458] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0459] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0460] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0461] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to HER2 antigen; (b) trastuzumab; and (c) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0462] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and optionally wherein the cancer is a gastric cancer. [0463] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and optionally wherein the cancer is a gastric cancer. [0464] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolumab; and optionally wherein the cancer is a gastric cancer. [0465] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0466] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0467] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0468] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2antigen; (b) trastuzumab; and (c) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0469] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0470] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0471] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0472] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy comprising docetaxel; and optionally wherein the cancer is a breast cancer. [0473] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy comprising paclitaxel; and optionally wherein the cancer is a breast cancer. [0474] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; (c) palbociclib; and (d) a hormone-based compound selected from any one or more of anastrozole, exemestane, letrozole, fulvestrant, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide, degarelix, toremifene, goserelin, triptorelin, histrelin, leuprolide, and tamoxifen citrate; and optionally wherein the cancer is a breast cancer. [0475] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; (c) abemaciclib; and (d) a hormone-based compound selected from any one or more of anastrozole, exemestane, letrozole, fulvestrant, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide, degarelix, toremifene, goserelin, triptorelin, histrelin, leuprolide, and tamoxifen citrate; and optionally wherein the cancer is a breast cancer. [0476] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; (d) atezolizumab; and (e) a chemotherapy agent comprising docetaxel; and optionally wherein the cancer is a breast cancer. [0477] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; (d) atezolizumab; and (e) a chemotherapy comprising paclitaxel; and optionally wherein the cancer is a breast cancer. [0478] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) fam-trastuzumab deruxtecan-nxki; and (c) durvalumab; and optionally wherein the cancer is a breast cancer. [0479] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) fam-trastuzumab deruxtecan-nxki; and (c) atezolizumab; and optionally wherein the cancer is a breast cancer. [0480] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) ado-trastuzumab emtansine; and (c) durvalumab; and optionally wherein the cancer is a breast cancer. [0481] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) ado-trastuzumab emtansine; and (c) atezolizumab; and optionally wherein the cancer is a breast cancer. [0482] In any of the aforementioned embodiments having a linker-payload (L- Dx) structure of:

the antibody comprises HC-CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10. In some embodiments, RX^* comprises a succinamide moiety and is bound to a cysteine residue of an antibody construct. In some embodiments, RX^* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of an antibody construct. [0483] In certain embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; and (b) pembrolizumab. [0484] In certain embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) fam-trastuzumab deruxtecan-nxki. [0485] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) ado-trastuzumab emtansine. [0486] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) a chemotherapy agent comprising pemetrexed; and (d) a chemotherapy agent comprising carboplatin; and optionally wherein the cancer is a NSCLC. [0487] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) pembrolizumab; and (c) a chemotherapy agent comprising pemetrexed; and (d) a chemotherapy agent comprising cisplatin; and optionally wherein the cancer is a NSCLC. [0488] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) atezolizumab; (c) bevacizumab; (d) a chemotherapy agent comprising carboplatin; and (e) a chemotherapy agent comprising paclitaxel; and optionally wherein the cancer is a NSCLC. [0489] In certain embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; and (b) nivolumab. [0490] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) trastuzumab. [0491] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) fam-trastuzumab deruxtecan-nxki. [0492] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) ado-trastuzumab emtansine. [0493] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) tucatinib. [0494] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) palbociclib. [0495] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; and (b) abemaciclib. [0496] In certain embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

wherein: A is an antibody; n is one; z is selected from 2 to about 8 or from 2 to about 4; and L and Dx have a structure of:

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to HER2 antigen; and (b) ribociclib. [0497] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; and (c) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0498] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0499] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0500] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and optionally wherein the cancer is a gastric cancer. [0501] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; and (c) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0502] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0503] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0504] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy regimen comprising leucovorin, fluorouracil, and cisplatin; and optionally wherein the cancer is a gastric cancer. [0505] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; and (c) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0506] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and optionally wherein the cancer is a gastric cancer. [0507] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and optionally wherein the cancer is a gastric cancer. [0508] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolumab; and optionally wherein the cancer is a gastric cancer. [0509] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0510] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0511] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy comprising capecitabine; and optionally wherein the cancer is a gastric cancer. [0512] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; and (c) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0513] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0514] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) nivolumab; and (d) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0515] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) atezolizumab; and (d) a chemotherapy regimen comprising capecitabine and oxaliplatin; and optionally wherein the cancer is a gastric cancer. [0516] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy comprising docetaxel; and optionally wherein the cancer is a breast cancer. [0517] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; and (d) a chemotherapy comprising paclitaxel; and optionally wherein the cancer is a breast cancer. [0518] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; (c) palbociclib; and (d) a hormone-based compound selected from any one or more of anastrozole, exemestane, letrozole, fulvestrant, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide, degarelix, toremifene, goserelin, triptorelin, histrelin, leuprolide, and tamoxifen citrate; and optionally wherein the cancer is a breast cancer. [0519] In further embodiments, a method of treating a HER2-expressing cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a HER2 antigen; (b) trastuzumab; (c) abemaciclib; and (d) a hormone-based compound selected from any one or more of anastrozole, exemestane, letrozole, fulvestrant, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide, degarelix, toremifene, goserelin, triptorelin, histrelin, leuprolide, and tamoxifen citrate; and optionally wherein the cancer is a breast cancer. [0520] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; (d) atezolizumab; and (e) a chemotherapy agent comprising docetaxel; and optionally wherein the cancer is a breast cancer. [0521] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) trastuzumab; (c) pembrolizumab; (d) atezolizumab; and (e) a chemotherapy comprising paclitaxel; and optionally wherein the cancer is a breast cancer. [0522] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) fam-trastuzumab deruxtecan-nxki; and (c) durvalumab; and optionally wherein the cancer is a breast cancer. [0523] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) fam-trastuzumab deruxtecan-nxki; and (c) atezolizumab; and optionally wherein the cancer is a breast cancer. [0524] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) ado-trastuzumab emtansine; and (c) durvalumab; and optionally wherein the cancer is a breast cancer. [0525] In further embodiments, a method of treating cancer comprises administering: (a) an antibody conjugate represented by Formula (I):

, or a salt thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody, wherein the antibody binds to a tumor associated antigen; (b) ado-trastuzumab emtansine; and (c) atezolizumab; and optionally wherein the cancer is a breast cancer. [0526] In any of the aforementioned embodiments having a linker-payload structure of:

, the antibody comprises HC-CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10. In some embodiments, RX^* comprises a succinamide moiety and is bound to a cysteine residue of an antibody construct. In some embodiments, RX^* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of an antibody construct. [0527] In any of the aforementioned embodiments, the cancer may be a HER2- expressing cancer, such as breast cancer, stomach/gastric cancer, colorectal cancer, non- small cell lung cancer (NSCLC), urothelial cancer, endometrial cancer, or ovarian cancer. [0528] In various embodiments, methods of treating HER2-expressing cancer are provided, comprising administering a conjugate provided herein, wherein the conjugate comprises an antibody that binds HER2, and an additional therapeutic agent comprising a kinase inhibitor, a therapeutic agent comprising an anti-HER2 antibody, or both the tyrosine kinase inhibitor and therapeutic agent comprising an anti-HER2 antibody. In some embodiments, the anti-HER2 antibody of the conjugate comprises the CDRs of pertuzumab, antigen binding fragment (e.g., variable regions) of pertuzumab, light and heavy chains of pertuzumab. In some embodiments, the anti- HER2 antibody of the conjugate comprises the CDRs of trastuzumab, antigen binding fragment (e.g., variable regions) of trastuzumab, light and heavy chains of trastuzumab. [0529] In some such embodiments, the anti-HER2 antibody of the conjugate comprises heavy chain (HC)-CDR1, HC-CDR2, HC-CDR3, light chain (LC)-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively. In further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain and light chain, wherein: (a) the heavy chain comprises HC-CDR1, HC-CDR2, and HC-CDR3 of SEQ ID NOs: 1-3, respectively, and comprises a heavy chain variable region (VH) having an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the V_H amino acid sequence of SEQ ID NO: 7; and (b) the light chain comprises LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 4-6, respectively, and a light chain variable region (V_L) having an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the VL amino acid sequence of SEQ ID NO: 8. In still further embodiments, the anti- HER2 antibody of the conjugate comprises a V_H comprising or consisting of the amino acid sequence of SEQ ID NO: 7 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 8. In yet further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain and light chain, wherein: (a) the heavy chain comprises HC-CDR1, HC-CDR2, and HC-CDR3 of SEQ ID NOs: 1-3, respectively, and comprises an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the heavy chain amino acid sequence of SEQ ID NO: 9; and (b) the light chain comprises LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 4-6, respectively, and an amino acid sequence that has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identity to the light chain amino acid sequence of SEQ ID NO: 10. In yet further embodiments, the anti-HER2 antibody of the conjugate comprises a heavy chain comprising or consisting of the amino acid sequence of SEQ ID NO: 9 and a light chain comprising or consisting of the amino acid sequence of SEQ ID NO: 10. [0530] In some such embodiments, the method comprises administering a conjugate comprising an antibody that binds HER2 and an additional therapeutic agent comprising an anti-HER2 antibody, wherein the anti-HER2 antibody of the conjugate and the anti-HER2 antibody of the additional therapeutic agent bind different epitopes of HER2. For example, the anti-HER2 antibody of the conjugate may comprise pertuzumab or the CDRs or antigen binding fragment (e.g., variable regions of pertuzumab), while the anti-HER2 antibody of the additional therapeutic agent comprises trastuzumab or a biosimilar thereof, or the CDRs or antigen binding fragment (e.g., variable regions of trastuzumab). [0531] In any of the aforementioned embodiments, the additional therapeutic agent is selected from trastuzumab, trastuzumab-qyyp, trastuzumab-pkrb, trastuzumab- dttb, trastuzumab-anns, trastuzumab-dkst, trastuzumab deruxtecan-nxki, ado- trastuzumab emtansine, trastuzumab duocarmazine, margetuximab, and zenocutuzumab (MCLA-128 (Merus)). [0532] In some embodiments, the additional therapeutic agent is a kinase inhibitor selected from a tyrosine kinase inhibitor and a serine/threonine kinase inhibitor. In some embodiments, the tyrosine kinase inhibitor is tucatinib, cabozantinib, afatinib, erlotinib, pyrotinib, neratinib, poziotinib, dacomitinib, gefitinib, lapatinib, osimertinib, larotrectinib, axitinib, lenvatinib, pazopanib, regorafenib, or sunitinib. In some embodiments, the serine/threonine kinase inhibitor is a CDK4/6 inhibitor, such as abemaciclib (Verzenio®), palbociclib (Ibrance®), or ribociclib (Kisqali®). [0533] In some embodiments, the additional therapeutic agent is a small molecule tyrosine kinase inhibitor that inhibits HER2. In some embodiments, the additional therapeutic agent is selected from tucatinib, cabozantinib, pyrotinib, neratinib, and poziotinib. [0534] In some embodiments, the additional therapeutic agents further comprises a chemotherapy agent, an immune checkpoint inhibitor, a biologic therapy such as a therapeutic antibody, a molecularly targeted therapy, chemotherapy protective agent, or any combination thereof. [0535] In some such embodiments, the immune checkpoint inhibitor is an antibody. In some such embodiments, the immune checkpoint inhibitor is an inhibitor of PD-1 and/or PD-L1, e.g., an anti-PD-1 and/or anti-PD-L1 antibody. Examples of anti-PD-1 and/or anti-PD-L1 antibodies include pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, and atezolizumab, or a biosimilar thereof. In some embodiments, the immune checkpoint inhibitor is an anti-PD1 antibody selected from pembrolizumab, nivolumab, and cemiplimab, or a biosimilar thereof. In some embodiments, the immune checkpoint inhibitor is an anti-PD-L1 antibody selected from avelumab, durvalumab, and atezolizumab, or a biosimilar thereof. [0536] In some such embodiments, the chemotherapy agent comprises a hormone-based compound, optionally wherein the hormone based compound comprises anastrozole, exemestane, letrozole, fulvestrant, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide, degarelix, toremifene, goserelin, triptorelin, histrelin, leuprolide, or tamoxifen citrate. [0537] In some such embodiments, the chemotherapy agent comprises a platinum coordination complex, optionally wherein the platinum coordination complex comprises cisplatin, oxaliplatin, or carboplatin. [0538] In some such embodiments, the chemotherapy agent comprises a folic acid analog, optionally wherein the folic acid analog comprises pemetrexed, methotrexate, or trimetrexate. [0539] In some such embodiments, the chemotherapy agent comprises a pyrimidine analog, optionally wherein the pyrimidine analog comprises fluorouracil, capecitabine, fluorodeoxyuridine, tezacitabine, gemcitabine, cytosine arabinoside, cytarabine, 5-azacytidine, or 2,2ʹ-difluorodeoxycytidine. [0540] In some such embodiments, the chemotherapy agent comprises a microtubule inhibitor, optionally wherein the microtubule inhibitor comprises paclitaxel, docetaxel, and eribulin. [0541] In some such embodiments, the chemotherapy protective agent comprises leucovorin (folinic acid), allpuronol, rasburicase, amifostine, dexrazoxane, or mesna. [0542] In any of the aforementioned embodiments, the linker-payload compound of the conjugate has a structure selected from:

on RX* represents the point of attachment to the residue of the antibody. In some embodiments, RX^* comprises a succinamide moiety and is bound to a cysteine residue of an antibody. In some embodiments, RX^* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of an antibody. [0543] In some embodiments, RX^* comprises a succinamide moiety and is bound to a cysteine residue of an antibody construct. [0544] In some embodiments RX^* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of an antibody construct. [0545] In certain aspects, the instant disclosure provides a method of treating HER2-expressing cancer comprising administering: (a) a conjugate having the following structure:

or a pharmaceutically acceptable salt thereof, wherein: Ab is an antibody, D is a TLR7 agonist of formula:

, wherein R⁴ is an alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl group comprising from 1 to 8 carbons, each J is hydrogen, each U is N, each t is 2, Q is not present, the dashed line represents a point of attachment of D to G1, and G1 is a bond; subscript a is an integer from 1 to 40; and subscript r is an integer from 1 to 10; and (b) a therapeutic antibody, a kinase inhibitor, a chemotherapy agent, or any combination thereof. In certain embodiments,

[0546] In certain embodiments, the instant disclosure provides a method of treating HER2-expressing cancer comprising administering: (a) a conjugate having the following structure:

, wherein Ab is trastuzumab; and (b) a PD-1 and/or PD-L1 inhibitor, optionally wherein the PD-1 and/or PD- L1 inhibitor comprises one or more of pembrolizumab, atezolizumab, and durvalumab. [0547] The combination therapies provided herein can be used in the methods described herein as a therapeutic, for example, as a treatment that can be administered in an effective regimen to a subject in need thereof to achieve a therapeutic effect. A therapeutic effect can be obtained in a subject by reduction, suppression, remission, alleviation or eradication of a disease state, including, but not limited to, one or more symptoms thereof. A therapeutic effect in a subject having a disease or condition, or exhibiting an early symptom thereof or exhibiting or otherwise suspected of being in or approaching an early stage of a disease or condition, can be obtained by a reduction, a suppression, a prevention, a delay, a remission, an alleviation or an eradication of the condition or disease, or pre-condition or pre-disease state. In various embodiments, the method comprises administering an effective regimen that results in a Tmax of the conjugate of greater than 4 hours following each administration of the conjugate. In some embodiments, the effective regimen results in a Tmax greater than 6 hours, greater than 8 hours, greater than 10 hours, greater than 12 hours, or greater than 15 hours following each administration of the conjugate. [0548] In certain embodiments, the methods include administration of an immune-stimulatory conjugate, or a pharmaceutical composition thereof, to a subject in need thereof in an effective regimen to activate, stimulate or augment an immune response against a disease treatable with a TLR agonist (e.g., cancer or a viral disease). The polypeptide of the conjugate recognizes an antigen associated with the disease or disease state, such as a tumor-associated antigen or liver cell antigen. [0549] In certain embodiments, the cancer to be treated with the therapeutic combinations provided herein is a solid tumor, such as a sarcoma, a carcinoma or lymphoma. In some such embodiments, the antibody of the conjugate recognizes an antigen on the target cells, such as a tumor-associated antigen. In some embodiments, the cancer is a HER2-expressing cancer and the antibody of the conjugate binds HER2. In some embodiments, the HER2-expressing cancer is selected from breast cancer, stomach/gastric cancer, colorectal cancer, non-small cell lung cancer (NSCLC), urothelial cancer, endometrial cancer, and ovarian cancer. In some aspects, the HER2 expressing cancer expresses HER2 at a level of 2+ or 3+ as determined by immunohistochemistry. [0550] In certain embodiments, the methods include administration of a combination therapy comprising a conjugate provided herein to a subject in need thereof to activate, stimulate or augment an immune response against tumor cells of a solid tumor, such as brain, breast, lung, liver, kidney, pancreatic, colorectal, ovarian, head and neck, bone, skin, mesothelioma, bladder, stomach/gastric, prostate, thyroid, uterine or cervical/endometrial cells. In some such embodiments, the polypeptide of the conjugate recognizes an antigen on the tumor cells. [0551] In some cases, treatment comprises reduced tumor growth. In some cases, treatment comprises tumor arrest. In some cases, combination therapy comprising a conjugate provided herein allows for dose reduction of an accompanying chemotherapy agent. [0552] In certain embodiments, the methods include administration of a combination therapy comprising a conjugate provided herein (e.g., including a TLR8 agonist antibody conjugate specific for a liver cell antigen, such as a liver cell antigen expressed on a liver cell infected with a virus) to a subject in need thereof to activate, stimulate or augment an immune response against viral infection, such as a chronic viral infection (e.g., HBV, HCV). In some embodiments, the liver cell antigen is a hepatocyte antigen. In further embodiments, the liver cell antigen is ASGR1 (asialoglycoprotein receptor 1), ASGR2 (asialoglycoprotein receptor 2), TRF2, UGT1A1, SLC22A7, SLC13A5, SLC22A1, or C9. In particular embodiments, the liver cell antigen is ASGR1, ASGR2, or TRF2. [0553] One of ordinary skill in the art would understand that the amount, duration and frequency of administration of a combination therapy described herein to a subject in need thereof depends on several factors including, for example but not limited to, the health of the subject, the specific disease or condition of the subject, the grade or level of a specific disease or condition of the subject, the additional therapeutics the subject is being or has been administered, and the like. [0554] In some aspects of practicing the methods described herein, the conjugates are administered in an effective regimen of at least two or at least three cycles. Each cycle can optionally include a resting stage between cycles. Cycles of administration can be of any suitable length. In some embodiments, each cycle is a week (7 days), 10 days, every two weeks (14 days or biweekly), every three week (21 days) or every four weeks (28 days). In some embodiments, each cycle is a month. In some embodiments, at least two doses of the immune-stimulatory conjugate are administered more than 7 days apart, or more than 10 days apart. In some embodiments, at least one dose of the conjugate is administered more than 7 days, or more than 10 days, after the initial dose of the conjugate. [0555] In certain embodiments, the total dose of the conjugate within a cycle is from about 0.1 to about 10 mg/kg. In some embodiments, the total dose is from about 0.5 to about 7.5 mg/kg. In some embodiments, the total dose is from about 0.5 to about 5 mg/kg. In some embodiments, the total dose is from about 0.5 to about 4 mg/kg. In some embodiments, the total dose is from about 0.5 to about 3.5 mg/kg. In some embodiments, the total dose is from about 0.5 to about 2 mg/kg. [0556] In some embodiments, an effective regimen comprises at least two cycles of administration of the conjugate to the subject and a total dose of greater than 0.4 mg/kg of the conjugate per cycle. [0557] Application of immune-stimulatory conjugates described herein shows substantial benefit in directing a subject’s own immune response to cells of a particular site of disease or disorder, such as cells associated with the disease or disorder. Activating or stimulating an immune response directed to targeted cells facilitates the reduction, inhibition of proliferation, inhibition of growth, inhibition of progression, inhibition of metastasis or otherwise inhibition up to and including in some cases clearance of the targeted cells. Thus, in some cases a targeted immune response activation or stimulation leads to inhibition of disease progression, or alleviation of at least one symptom of a manifest disease in a patient, up to and in some cases including complete elimination of from one symptom to an entire disease state in a subject. [0558] In particular, the methods disclosed herein are well suited for use with immune stimulatory conjugates, such as immune stimulatory conjugates that direct an immune response in a subject to a particular disorder or disease location, cell type or cell. Accordingly, practice of some methods herein comprises selection of a suitable subject such as a subject to be subjected to or undergoing a treatment with a conjugate that directs a benzazepine or benzazepine-like compound of the conjugate to a particular disorder or disease site, cell type or cell. Often, the subject is selected for practice of the method due to having at least one symptom of a disease or disorder, or projected to develop at least one symptom of a disease or disorder (such as a subject in remission and at risk for relapse), suitable for treatment by a conjugate as disclosed herein. Some diseases are selected not based upon or not based solely on disease type, but upon detection or presence of a suitable epitope on a tumor, cell type or particular cell that facilitates localization of an immune-stimulatory conjugate to the epitope. EXAMPLES [0559] The following examples are included to further describe some embodiments of the present disclosure and should not be used to limit the scope of the disclosure. The examples are not intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (for example, amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric. [0560] While aspects of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that such aspects are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the aspects of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby. EXAMPLE 1: HER2-TLR8 CONJUGATE ACTIVATES DENDRITIC CELLS AS MEASURED BY UPREGULATION OF SURFACE MARKERS SUCH AS PD-L1 AND CD86 [0561] The expression of activation markers, including CD86, CD40, CD80 and PD-L1, on human dendritic cells (DCs) following contact with a HER2-TLR8 conjugate in the presence of HER2-expressing tumor cells was determined. HER2- TLR8 comprises an anti-HER2 antibody comprising the heavy and light chains of SEQ ID NOs: 9 and 10, respectively, conjugated to a TLR8-linker having the structure

. Briefly, myeloid DCs were isolated from human blood using the EasySep^TM Human Myeloid DC Enrichment Kit (StemCell Technologies, Catalog #19061). Isolated dendritic cells were plated with HER2-expressing BT474 tumor cells (ATCC) at a 2:1 ratio in the presence of titrating concentrations of HER2-TLR8 conjugate or HER2 mAb. After 24 hours, the cells were collected, washed and stained on ice with a collection of commercially available antibodies conjugated to fluorophores directed against PD-L1, CD86, CD80, CD40, CD45, and HLA-DR per the manufacturer’s recommended protocol. After washing to remove unbound antibody-fluorophore molecules, the stained cells are subjected to FACS analysis using a Celesta flow cytometer (BD Biosciences) with gating on live cells. The output was analyzed by FlowJo v10.2 software (FlowJo LLC). [0562] The addition of HER2-TLR8 conjugate to the co-culture assays containing BT474 cells resulted in the upregulation of all activation markers, including PD-L1, on the DC (see Figures 1A and 1B). Activation marker expression, including PD-L1, was not increased above baseline in co-cultures with the unconjugated HER2 mAb. These data demonstrate that agonism of TLR8 by the HER2-TLR8 composition result in the activation of DCs, including the upregulation of PD-L1. PD-L1 is the ligand for the inhibitory receptor PD-1, a receptor expressed on T cells and other immune cells. EXAMPLE 2: HER2-TLR8 INDUCES THE PRODUCTION OF IFN-γ A POTENT INDUCER OF PD-L1 UPREGULATION [0563] Numerous studies have shown the upregulation of PD-L1, a T cell checkpoint molecule, by IFN-γ on tumor cells in the tumor microenvironment. (Abiko, Br J Cancer.2015 Apr 28;112(9):1501-9; Garcia-Diaz A, Cell Rep.2017 May 9;19(6):1189-1201; Mimura, Cancer Sci.2018 Jan;109(1):43-53). To determine whether a HER2-TLR8 conjugate can induce production of IFN-γ by human PBMCs in the presence of HER2 expressing tumor cells, the following experiment was conducted. Human whole blood was obtained from Bloodworks Northwest (Seattle, WA) and collected in 10mL EDTA tubes. Human PBMCs were then isolated from the whole blood by Ficoll gradient centrifugation and resuspended in assay media (RPMI-1640 Medium supplemented with 10% Fetal Bovine Serum, 1mM Sodium Pyruvate, 1X GlutaMAX-1, 1X Non-Essential Amino Acids, 10mM HEPES and 0.5% Penicillin/Streptomycin; all from Gibco). Isolated PBMCs were resuspended in assay media and plated in 96-well flat bottom microtiter plates (125,000/well). HER2- expressing tumor cells were removed from tissue culture flasks with HyQTASE (Hyclone), washed twice, resuspended in assay media and were added to the microtiter plates (25,000/well) along with titrating concentrations of HER2-TLR8 conjugate. After overnight culture, supernatants were harvested, and IFN-γ levels were determined by a Meso Scale Discovery) analyte detection kit. [0564] As shown in Figure 2, HER2-TLR8 conjugate stimulated IFN-γ production from huPBMCs in the presence of HER23+ (SK-BR-3) and HER22+ (MDA-453) expressing cells. In contrast, there was no IFN-γ production from huPBMCs in the presence of tumor cells lacking the expression of HER2 (MDA-468). These data indicate that the combination of HER2-TLR8 with a T cell checkpoint inhibitor, such as an anti-PD-1 small molecule or antibody, should provide enhanced efficacy. EXAMPLE 3: RATIONALE FOR HER2-TLR7 CONJUGATE AS A MOUSE SURROGATE FOR HER2-TLR8 [0565] Rodents do not express a functional homolog of TLR8 and attempts by multiple groups to generate relevant human TLR8 transgenic mice have been unsuccessful (Wang, J Biol Chem.2006 Dec 8;281(49):37427-34; Guiducci, J Exp Med.2013 Dec 16;210(13):2903-19). Like TLR8 in human, and in contrast to TLR7 in human, TLR7 in mouse is expressed in myeloid cells. Using RNA expression data from the publicly available database Haemopedia, Figure 3 demonstrates the similarity in expression between TLR7 in mouse and TLR8 in human in dendritic cells and macrophages. Further, and as anticipated by similarity in expression and structure between mouse TLR7 and human TLR8, stimulation of TLR7 in murine myeloid cells results in activation that mirrors that observed with TLR8 stimulation in human myeloid cells (Clarke, J. Cytokine Interferon Res.2009, Feb;29(2):113-26; Gordon, J. Immunol. 2005 Feb 1;174(3):1259-68). A HER2-TLR7 mouse surrogate consisting of a TLR7 agonist conjugated to an anti-human HER2 antibody of the mouse IgG2a isotype (HER2-TLR7) was generated for use in in vivo pharmacology studies. In vitro studies with mouse myeloid cells derived from bone marrow demonstrate that the HER2-TLR7 mouse surrogate has an EC50 of ~ 0.5nM, equivalent to the potency of HER2-TLR8 conjugates on human myeloid cells (data not shown). These studies and findings collectively support HER2-TLR7 conjugate as a surrogate molecule for HER2-TLR8 in mouse. As such, HER2-TLR7 was evaluated for activity in syngeneic mouse models. EXAMPLE 4: TREATMENT WITH HER2-TLR7 SURROGATE DISPLAYS DOSE-DEPENDENT SINGLE AGENT EFFICACY IN A XENOGRAFT MOUSE MODEL [0566] The single agent efficacy in mice bearing HER2-expressing tumors with the HER2-TLR7 agonist conjugate (i.e., surrogate for human HER2-TLR8 conjugate) was examined. Briefly, SCID mice (Taconic Biosciences, Albany, NY) were inoculated subcutaneously with about 1 x 10⁶ NCI-N87 cells (HER2+ tumorigenic human epithelial cells) to generate the NCI-N87 xenograft mouse model. Once palpable, tumor dimensions were measured by calipers and volume was calculated using the equation: Volume = (L x W x H x 0.5). When tumors reached approximately 90 mm³ (Day 0), mice were administered 5 mg/kg, 2 mg/kg, or 1 mg/kg HER2-TLR7 or unconjugated HER2-IgG2a mAb every 7 days for 4 doses. The HER2-TLR7 comprises anti-HER2 antibody variable domains comprising the heavy chain CDRs of SEQ ID NOs: 1-3 and light chain CDRs of SEQ ID NOs: 4-6, conjugated to a TLR7 agonist- linker having the structure:

. An isotype control mAb (BioXcell, West Lebanon, NH), matched to the unconjugated HER2-IgG2a mAb, was dosed at 5 mg/kg on the same schedule. Tumor volumes were recorded 3 times per week. [0567] Treatment with the HER2-TLR7 surrogate resulted in significant inhibition of tumor growth at all doses tested (see Figures 4E, 4F, and 4G) as compared to the isotype antibody or unconjugated HER2-IgG2a antibody controls (see Figures 4A, 4B, 4C, and 4D). Like unconjugated HER2-IgG2a antibody treated group, the mice treated with IgG2a-TLR7 showed no delay in tumor growth (see Figures 4H, 4J, and 4K). These results demonstrate that the HER2-TLR7 surrogate is efficacious across a range of dose levels with robust single agent efficacy at dose levels as low as 1-2 mg/kg in vivo. EXAMPLE5: IN VIVO TREATMENT WITH A HER2-TLR7 SURROGATE RESULTS IN PD-L1 UPREGULATION ON THE SURFACE OF TUMOR CELLS [0568] The effect of treatment of mice bearing HER2-expressing tumors with the HER2-TLR7 conjugate surrogate, on PD-L1 expression on the surface of tumor cells was examined. Briefly, female BALB/c mice (Jackson Laboratory) were inoculated subcutaneously with 5x10⁵ human HER2-expressing CT26 tumor cells. Once palpable, tumor dimensions were measured by calipers and volume was calculated using the following equation: Volume = (L x W x H x 0.5). When tumors reached an average of approximately 200 mm³ (Day 0), mice were administered 5 mg/kg HER2-TLR7 or HER2 mAb (matched, unconjugated antibody control) subcutaneously on days 0, 2, and 4. At 48 hours post-doses one and three, tumors were harvested and dissociated using the Miltenyi mouse tumor digest kit. Single cell suspensions were assayed for PD-L1 expression using flow cytometry. [0569] As shown in Figures 5A and 5B, tumor cells (identified as CD45 negative, forward scatter high) showed a significant increase in PD-L1 expression at both time points evaluated. These findings provide evidence that combination with immune checkpoint inhibition could enhance efficacy. EXAMPLE 6. COMBINATION OF HER2-TLR7 SURROGATE AND IMMUNE CHECKPOINT INHIBITOR LEADS TO INCREASED TH1 CYTOKINES AND CHEMOKINES. [0570] The effect of treating tumor bearing mice with a combination of HER2- TLR7 conjugate surrogate and anti PD-1 on IFN-γ and IP-10 expression was determined. Briefly, female BALB/c mice (Jackson Laboratory) were inoculated subcutaneously in the mammary fat with 1x10⁵ human HER2-expressing EMT6 tumor cells. Once palpable, tumor dimensions were measured by calipers and volume was calculated using the equation: Volume = (L x W x H x 0.5). When tumors reached approximately 97mm³ (Day 0), mice were given one dose of 10 mg/kg HER2-TLR7, HER2 mAb (matched, unconjugated antibody control), rat anti-PD1 (clone RMP1-14) or isotype controls, alone or in combination. Two or seven days later, tumors were excised, weighed placed in 500mL RPMI (Gibco) and mechanically dissociated on ice. The resulting supernatants were analyzed by Luminex (Millipore) for intratumoral cytokines and chemokines. Data is expressed as picogram of analyte per gram of starting tissue. [0571] Figure 6A shows that IP10 production was significantly increased in the combination treated group at Day 2 compared to HER2-TLR7 or anti PD-1 treated groups. Similarly, IFN-γ production was augmented at Day 2 in tumors of mice treated with combination of HER2-TLR7 with anti-PD-1 compared to HER2-TLR7 treated mice (Figure 6B). This amplification of IFN-γ was sustained at Day 7 after treatment. These data indicate that the combination of an immune checkpoint inhibitor with HER2-TLR8 is expected to lead to enhanced chemokine and cytokine production by immune cells. EXAMPLE 7. ANTI-TUMOR RESPONSE OF HER2-TLR7 SURROGATE IS ENHANCED WHEN COMBINED WITH ANTI-PD1 [0572] The anti-tumor efficacy induced by single agent HER2-TLR7 conjugate mouse surrogate (HER2-TLR7) was examined in combination with anti-PD1 therapy. Female BALB/c mice (Jackson Laboratory) were inoculated subcutaneously with 1x10⁵ human HER2-expressing EMT6 tumor cells. Once palpable, tumor dimensions were measured by calipers and volume was calculated using the following equation: Volume = (L x W x H x 0.5). When tumors reached approximately 90 mm³ (Day 0), mice were given 10 mg/kg HER2-TLR7, HER2 mAb (naked antibody control), rat anti- PD1 (clone RMP1-14) or isotype controls, alone or in combination, every 7 days for a total of 3 doses. Tumor volume was recorded 3 times per week and mice were euthanized when tumors reached 1,500 mm³. [0573] Figure 7D spider plots show that this model is refractory to single agent anti-PD1 therapy with no survival benefit or growth inhibition over the isotype control group (see Figure 7A). In contrast, treatment with HER2-TLR7 surrogate inhibited tumor growth with 60% of mice surviving to day 42 (see Figure 7C). Moreover, the combination of HER2-TLR7 with anti-PD1 therapy greatly enhanced the effect of either agent alone with 90% of mice surviving to day 42 (see Figure 7F). EXAMPLE 8. HER2-TLR8 AND A TRASTUZUMAB-LIKE MONOCLONAL ANTIBODY, HUMANIZED 4D5, BIND TO DIFFERENT HER2 EPITOPES [0574] The trastuzumab-like monoclonal antibody, humanized 4D5 mAb (hz4D5), was produced using the ExpiCHO expression system as described in the manufacturer’s protocol (Thermo Fisher Scientific). Briefly, 6x10⁶ ExpiCHO-S cells per ml were cultured in ExpiCHO Expression Medium followed by addition of ExpiFectamine CHO/plasmid DNA complexes (1μg DNA/ml) directly to cells. ExpiCHO Feed and Enhancer were added the day after transfection to support long- term, high-density transient transfections and to enhance protein production. The cell culture supernantants were harvested on Day 7 following transfection. Hz4D5 from the ExpiCHO supernatants were purified to homogeneity over HiScreen MabSelect SuRe protein A column on GE AKTA Pure^TM system. It was confirmed for purity on Size Exclusion Chromatography using Agilent 1260 Infinity machine. [0575] Analysis of simultaneous versus competitive binding of HER2-TLR8 and hz4D5 to human HER2 extra-cellular domain (ECD) was performed using an Octet Red 96TM instrument (ForteBio). The experiments were performed using the following steps: (1) Regeneration and neutralization of penta-his sensor in 10mM glycine-HCl (pH 1.5) and PBS/0.1%BSA/0.02%Tween20 (pH 7.4), respectively in triplicate; (2) baseline acquisition (30s); (3) immobilization of monomeric human HER2 ECD with 10x histidine tag to penta-his sensor at a concentration of 5μg/mL in PBS/0.1%BSA/0.02%Tween20 (180s); (4) second baseline acquisition (60s); (5) association of test article #1 (HER2-TLR8 or hz4D5) at 25 μg/mL until saturation (300s); (6) third baseline acquisition (15s); (7) association of test article #2 (HER2- TLR8 or hz4D5) at 25 μg/mL (300s); (8) dissociation in baseline buffer (60s). The data were analyzed using Octet Data Analysis Software HT 9.0TM (ForteBio). [0576] The interactions of HER2-TLR8 and hz4D5 with monomeric human HER2 ECD were evaluated using Octet Red 96TM in 2 orientations. Figure 8A shows Orientation #1 whereby HER2-TLR8 binds to HER2 ECD until saturation and then either HER2-TLR8 or hz4D5 is added. Figure 8B shows Orientation #2 whereby hz4D5 binds to HER2 ECD until saturation and then either hz4D5 or HER2-TLR8 is added. Affinity of either test article to immobilized HER2 ECD is subject to 2:1 binding avidity and no dissociation of test article #1 is observed in the third baseline step. [0577] Figure 8A shows that additional mass is observed when hz4D5 is added to a HER2-TLR8 saturated surface, indicating additional binding sites are available, whereas no additional mass is observed when HER2-TLR8 is added to an already HER2-TLR8 saturated surface, indicating all HER2-TLR8 binding sites are taken up. Figure 8B shows that additional mass is observed when HER2-TLR8 is added to a hz4D5 saturated surface, indicating additional binding sites are available, whereas no additional mass is observed when hz4D5 is added to an already hz4D5 saturated surface, indicating all hz4D5 binding sites are taken up. Together, these two orientations confirm that HER2-TLR8 and hz4D5 do not compete for binding space on HER2 ECD when either site is saturated with the other test article. Furthermore, this data confirmed that HER2-TLR8 and hz4D5 are able to bind simultaneously to human HER2 ECD. EXAMPLE 9. HER2-TLR8 AGONIST CONJUGATE DOES NOT IMPEDE FUNCTION OF TRASTUZUMAB- LIKE ANTIBODY, HZ4D5, IN VITRO [0578] The ability of trastuzumab to inhibit HER2-dependent tumor cell growth in vitro has been extensively described in the literature (see, e.g., Yamashita-Kashima et al., Clin. Cancer Res.17:5060, 2011; Ko et al., Mol. Oncol.9:398, 2015: Nami et al., Cancers 10:342, 2018). SBT6050 and hz4D5 (trastuzumab binding domain) recognize distinct, non-overlapping epitopes on HER2. Briefly, BT-474 tumor cells were cultured in the presence of HER2-TLR8 conjugate, negative control mAb conjugated to TLR8 agonist (IgG1-TLR8), or isotype control mAb alone or in combination with 1:1 ratio of trastuzumab-like monoclonal antibody hz4D5. Cells were incubated for 3 days and tumor cell viability was measured using Cell Titer-Glo® Luminescent Cell Viability Kit (Promega). Results are expressed as a percentage decrease in viability compared to BT- 474 tumor cells grown in media alone. [0579] Antibody hz4D5 showed significant anti-proliferative effects on the growth of BT-474 tumor cells, whereas the combination of hz4D5 and HER2-TLR8 agonist conjugate increased this effect (Figure 9). HER2-TLR8 agonist conjugate alone had no effect on the growth of BT474 tumor cells (Figure 9). In short, HER2-TLR8 agonist conjugate does not affect the ability of hz4D5 to inhibit the growth of HER2 positive tumor cells in vitro. These results indicate that trastuzumab function will likely be maintained, and even enhanced, when used in combination with HER2-TLR8 agonist conjugate in vivo. EXAMPLE 10. COMBINING HER2-TLR8 CONJUGATE WITH A TRASTUZUMAB-LIKE MONOCLONAL ANTIBODY AUGMENTS RELEASE OF PBMC TNF-Α AND IFN-Γ PRODUCTION IN THE PRESENCE OF HER2 EXPRESSING TUMOR CELLS [0580] Production of TNF-α and IFN-γ from PBMC co-cultured with HER2 positive tumor cell lines contacted with a HER2-TLR8 conjugate and hz4D5, a trastuzumab-like monoclonal antibody, was examined. The HER2-TLR8 conjugate does not cross-block binding or the function of the trastuzumab-like monoclonal antibody (see Examples 8 and 9). Peripheral blood mononuclear cells (PBMC) were isolated from normal human donor peripheral blood using SepMate™-50 PBMC Isolation Tubes (STEMCELL Technologies) according to manufacturers instructions. Isolated PBMC were cultured with the HER2-expressing tumor cell lines NCI-N87, BT-474, HCC-1954 (ATCC) or the HER2-negative tumor cell line MDA-MB-468 (ATCC) at a 5:1 ratio in the presence of titrated concentrations of a HER2-TLR8 conjugate, the matched unconjugated HER2 mAb control, a trastuzumab-like humanized monoclonal antibody (hz4D5) or an isotype control monoclonal antibody. After 24 hours the cell-free supernatants were collected and stored at -80ºC prior to analysis. TNF-α levels in the cell-free supernatants were quantified using the TNF-α (human) AlphaLISA Detection Kit (Perkin Elmer) according to manufacturer’s instructions. IFN-γ levels in the cell-free supernatants were quantified using the U- PLEX Biomarker Group 1 (Human) Multiplex Assay (Meso Scale Diagnostics) according to manufacturer’s instructions. [0581] Representative data is shown in Figure 10A for TNF-α and Figure 10B for IFN-γ. Figure 10A shows HER2-TLR8 induced TNF-α production is augmented in PBMC cultured with the HER2-expressing tumor cell lines NCI-N87, BT-474 or HCC- 1954 when combined with the trastuzumab-like monoclonal antibody hz4D5 compared to the combination of HER2-TLR8 and an isotype control. No TNF-α production was observed with the combination of hz4D5 and the matched unconjugated HER mAb indicating that TLR8 agonism is required for TNF-α release. TNF-α production was observed with the HER2-negative tumor cell line MDA-MB-468 only in cultures containing HER2-TLR8 at the highest concentrations tested indicating that the activity is also dependent upon HER2. As observed for TNF-α, Figure 10B shows IFN-γ production is augmented in PBMC cultured with the HER2-expressing tumor cell line NCI-N87 when HER2-TLR8 is combined with the trastuzumab-like monoclonal antibody hz4D5 compared to the combination of HER2-TLR8 and an isotype control monoclonal antibody. [0582] Taken together these data demonstrate augmented TNF-α and IFN-γ production by the combination of HER2-TLR8 and the trastuzumab-like monoclonal antibody hz4D5 over the effects observed with HER2-TLR8 alone. These effects are mediated by the TLR8 agonist conjugate rather than by HER2-TLR8 binding to a different epitope than 4D5 and suggest combining HER2-TLR8 with a clinical HER2- targeting antibody, such as trastuzumab, may increase therapeutic efficacy in certain tumor settings. EXAMPLE 11: COMBINATION OF HER2-TLR7 SURROGATE WITH A TRASTUZUMAB-LIKE MONOCLONAL ANTIBODY, HUMANIZED 4D5 (HZ4D5), IS EFFICACIOUS IN A XENOGRAFT MOUSE MODEL [0583] This example shows that the robust single agent efficacy, including an 80% cure rate, achieved with the HER2-TLR7 mouse surrogate conjugate at 10 mg/kg is not impeded by combination with the trastuzumab-like monoclonal antibody, hz4D5. The trastuzumab-like monoclonal antibody, humanized 4D5 mAb (hz4D5), does not cross-block HER2-TLR7 binding, suggestive of binding to different regions of HER2. SCID mice (Charles River) were inoculated subcutaneously with 1 x 10⁶ NCI-N87 (HER2+) tumor cells. Once palpable, tumor dimensions were measured by calipers and volume was calculated using the equation: Volume = (L x W x H x 0.5). When tumors reached approximately 90 mm³ (Day 0), mice were given 10 mg/kg HER2-TLR7, HER2 mAb (matched, unconjugated antibody control), or isotype controls (BioXcell), alone or in combination with 10 mg/kg hz4D5, every 7 days for a total of 4 doses. Tumor volume was recorded 3 times per week. [0584] As shown in Figures 11A-11F, mice treated with isotype controls, the unconjugated HER2 mAb, or hz4D5 showed no delay in tumor growth. Combination of HER2 mAb with hz4D5 initially showed tumor growth inhibition, but the tumors eventually grew out. However, HER2-TLR7 as a single agent resulted in profound efficacy with 8/10 mice completely clearing their tumors by Day 66 at this dose level. Importantly, the combination of HER2-TLR7 with hz4D5 had no adverse effect on the single agent efficacy of HER2-TLR7 at this dose level. EXAMPLE 12. COMBINATION OF A TRASTUZUMAB-LIKE MONOCLONAL ANTIBODY, HUMANIZED 4D5 MAB (HZ4D5), AND LOW DOSE HER2-TLR7 SURROGATE CONJUGATE DEMONSTRATES ENHANCED EFFICACY OVER SINGLE AGENTS IN A XENOGRAFT MOUSE MODEL [0585] To examine whether the efficacy of HER2-TLR7 mouse surrogate conjugate combined with the trastuzumab-like monoclonal antibody, hz4D5, was increased as compared to either agent administered alone, a low dose of the HER2- TLR7 mouse surrogate conjugate was used. Briefly, SCID mice (Charles River) (n = 10) were inoculated subcutaneously with about 1x10⁶ NCI-N87 (HER2+) tumor cells. Once palpable, tumor dimensions were measured by calipers and volume and calculated using the equation: Volume = (L x W x H x 0.5). When tumors reached approximately 100 mm³ (Day 0), mice were dosed with HER2-TLR7 mouse surrogate conjugate (1 mg/kg), matched unconjugated HER2-IgG2a mAb (1 mg/kg), or isotype mAb control matched to unconjugated HER2-IgG2a mAb (5 mg/kg) alone or in combination with the trastuzumab-like monoclonal antibody hz4D5 (5 mg/kg) every 7 days for a total of 3 doses. Tumor volume was recorded 3 times per week. [0586] HER2-TLR7 administered at the low dose in this example allowed for evaluation of efficacy in combination with the trastuzumab-like monoclonal antibody, hz4D5, as compared to the single agents alone. Mice treated with unconjugated HER2- IgGa mAb, hz4D5, or HER2-TLR7 surrogate showed some delay in tumor growth compared to the isotype control group, but the tumors eventually grew. However, mice treated with the HER2-TLR7 surrogate in combination with hz4D5 showed a significant reduction in tumor growth (Figure 12F) compared to all other treated groups (Figures 12A-E). These data show that the HER2-TLR7 surrogate in combination with trastuzumab-like monoclonal antibody, hz4D5 results in enhanced efficacy over the single agents alone. In addition, these data indicate that clinical evaluation of HER2- TLR8 agonist conjugates of this disclosure as a single agent and in combination with trastuzumab in relevant HER2-expressing tumor types is warranted. [0587] While aspects of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that such aspects are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the aspects of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Table of Anti-HER2 Antibody Sequences

The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, including U.S. Patent Application No.62/908,881, filed October 1, 2019, U.S. Patent Application No.62/935,789, filed November 15, 2019, and U.S. Patent Application No.63/018,615, filed May 1, 2020, are incorporated herein by reference, in their entirety. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications to provide yet further embodiments. These and other changes can be made to the embodiments in light of the above- detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.

Claims

CLAIMS WHAT IS CLAIMED IS: 1. A method of treating cancer or viral infection, comprising administering to a subject with cancer or viral infection a conjugate and an immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1; wherein the conjugate is represented by Formula (I): wherein:

A is an antibody that binds a tumor associated antigen or a liver cell antigen, L is a linker; D_x is a TLR8 agonist, wherein the TLR8 agonist is a benzazepine compound; n is selected from 1 to 20; and z is selected from 1 to 20.

2. The method of claim 1, wherein the immune checkpoint inhibitor is an antibody.

3. The method of claim 1 or 2, wherein the immune checkpoint inhibitor is an anti-PD-1 antibody or an anti-PD-L1 antibody.

4. The method of claim 3, wherein the anti-PD-1 antibody is selected from pembrolizumab, nivolumab, cemiplimab, and biosimilars thereof.

5. The method of claim 3, wherein the anti-PD-L1 antibody is selected from avelumab, durvalumab, atezolizumab, and biosimilars thereof.

6. The method of any one of claims 1-5, wherein n is 1 and z is from 1 to 8.

7. The method of any one of claims 1-6, wherein the TLR8 agonist is a compound of Category A, Formula (IIB):

or a pharmaceutically acceptable salt thereof, wherein: L¹⁰ is -X¹⁰-; L² is selected from -X²-, -X²-C1-6 alkylene-X²-, -X²-C_2-6 alkenylene-X²-, and - X²-C_2-6 alkynylene-X²-, each of which is optionally substituted on alkylene, alkenylene or alkynylene with one or more R¹²; X¹⁰ is selected from -C(O)-, and -C(O)N(R¹⁰)-*, wherein * represents where X¹⁰ is bound to R⁵; X² at each occurrence is independently selected from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, -C(O)N(R¹⁰)C(O)N(R¹⁰), -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)- , -S(O)₂-, -OS(O)-, -S(O)O-, -S(O), -OS(O)₂-, -S(O)₂O, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from hydrogen; and C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R⁵ is selected from unsaturated C4-8 carbocycle; bicyclic carbocycle; and fused 5-5, fused 5-6, and fused 6-6 bicyclic heterocycle, wherein R⁵ is optionally substituted and wherein substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁵ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁰ is independently selected at each occurrence from hydrogen, -NH2, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C_3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl; wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle; R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle.

8. The method of any one of claims 1-7, wherein the TLR8 agonist is a compound of Category A, Formula IIC:

or a pharmaceutically acceptable salt thereof, wherein: R¹ and R² are hydrogen; L² is -C(O)-; R⁴ is -N(R¹⁰)₂; R¹⁰ is independently selected at each occurrence from hydrogen, -NH2, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH2C6H5, -NHC(O)OCH2C6H5, C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L¹⁰ is -C(O)N(R¹⁰)-*, wherein * represents where L¹⁰ is bound to R⁵; and R⁵ is a fused 5-5, fused 5-6, or fused 6-6 bicyclic heterocycle, wherein R⁵ is optionally substituted and wherein substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl.

9. The method of claim 8, wherein R⁴ is -N(C_1-4 alkyl)₂ and L¹⁰ is -C(O)N(H)-*.

10. The method of claim 8 or 9, wherein:

11. The method of any one of claims 1 to 10, wherein the TLR8 agonist is selected from:

pharmaceutically acceptable salts thereof.

12. The method of any one of claims 1-11, wherein Dx is a compound of Formula (IVB):

or a pharmaceutically acceptable salt thereof, wherein: L¹² is selected from -X³-, -X³-C1-6 alkylene-X³-, -X³-C_2-6 alkenylene-X³-, and -X³-C_2-6 alkynylene-X³-, each of which is optionally substituted on alkylene, alkenylene, or alkynylene with one or more substituents independently selected from R¹²; L²² is independently selected from -X⁴-, -X⁴-C1-6 alkylene-X⁴-, -X⁴-C_2-6 alkenylene-X⁴-, and -X⁴-C_2-6 alkynylene-X⁴-, each of which is optionally substituted on alkylene, alkenylene, or alkynylene with one or more substituents independently selected from R¹⁰; X³ and X⁴ are independently selected at each occurrence from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, -C(O)N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-, -S(O)₂-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)₂-, -S(O)₂O-, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from L³, and hydrogen; and C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl, each of which is optionally bound to L³ and each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R⁴ and R⁸ are independently selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally bound to L³ and each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ and R⁸ is optionally bound to L³ and each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ and R⁸ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁰ is independently selected at each occurrence from L³, hydrogen, -NH2, -C(O)OCH₂C₆H₅; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO₂, -NH₂, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L³ is a linker moiety, wherein there is at least one occurrence of L³; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C_3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl; wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle; R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴, and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C3-7 carbocycle.

13. The method of any one of claims 1-12, wherein Dx is a compound of Formula (IVC):

or a pharmaceutically acceptable salt thereof, wherein: R¹ and R² are hydrogen; L²² is -C(O)- R⁴ is -N(R¹⁰)₂; R¹⁰ is independently selected at each occurrence from hydrogen, -NH₂, -C(O)OCH2C6H5; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L¹² is -C(O)N(R¹⁰)-*, wherein * represents where L¹² is bound to R⁸; R⁸ is an optionally substituted fused 5-5, fused 5-6, or fused 6-6 bicyclic heterocycle bound to linker moiety L³, and wherein optional substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl.

14. The method of claim 13, wherein R⁴ is -N(C_1-4 alkyl)₂ and L¹² is -C(O)N(H)-*.

15. The method of claim 13 or 14, wherein:

.

16. The method of any one of claims 1-15, wherein L and Dx together have a structure selected from:

,

and salts thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody.

17. The method of claim 16, wherein L and Dx together have a structure selected from:

and salts thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein

on RX* represents the point of attachment to the residue of the antibody.

18. The method of claim 16 or 17, wherein RX* comprises a succinamide moiety and is bound to a cysteine residue of the antibody.

19. The method of claim 16 or 17, wherein RX* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of the antibody.

20. The method of any one of claims 1-19, wherein the tumor antigen is selected from HER2, Nectin4, MSLN, LIV-1, MUC16, CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, CEACAM8, CEACAM16, CEACAM18, CEACAM19, CEACAM20, CEACAM21, VEGFR1, VEGFR2, MUC1, PSMA, PSA, MUC-2, and LRRC15.

21. The method of any one of claims 1-20, wherein the tumor associated antigen is selected from: a) an antigen present on breast cancer, wherein the antigen is optionally selected from HER2, LIV-1, CDH3 (p-cadherin), MUC1, Sialo-epitope CA6, PTK7, GPNMB, LAMP-1, LRRC15, ADAM12, EPHA2, TNC, LYPD3, EFNA4, Nectin-4, and CLDN6; b) an antigen present on lung cancer, wherein the antigen is optionally selected from mesothelin, HER2, EGFR, PD-L1, MSLN, LY6K, CD56, PTK7, FOLR1, DLL3, SLC34A2, CECAM5, MUC16, LRRC15, ADAM12, EGFRvIII, LYPD3, EFNA4, Nectin-4, and MUC1; c) an antigen present on stomach/gastric cancer, wherein the antigen is optionally selected from HER2, EPHB2, TMEM238, CECAM5, and EFNA4; d) an antigen present on colorectal cancer, wherein the antigen is optionally selected from EPHB2, TMEM238, CECAM5, LRRC15, ADAM12, EFNA4, Nectin-4, and GPA33; e) an antigen present on liver cancer, wherein the antigen is optionally selected from GPC3, EPCAM, and CECAM5; f) an antigen present on kidney cancer, wherein the antigen is optionally selected from HAVCR1, ENPP3, CDH6, CD70, and cMET; g) an antigen present on ovarian cancer, wherein the antigen is optionally selected from MUC16, MUC1, MSLN, FOLR1, sTN, VTCN1, HER2, PTK7, FAP, TMEM238, LRRC15, CLDN6, SLC34A2, and EFNA4; h) an antigen present on head and neck cancer, wherein the antigen is optionally selected from LY6K, PTK7, LRRC15, ADAM12, LYPD3, EFNA4, Nectin- 4, and TNC; i) an antigen present on bone cancer, wherein the antigen is optionally selected from EPHA2, LRRC15, ADAM12, GPNMB, TP-3, and CD248; j) an antigen present on mesothelioma, wherein the antigen is optionally MSLN; k) an antigen present on bladder cancer, wherein the antigen is optionally selected from LY6K, PTK7, UPK1B, UPK2, TNC, Nectin4, SLITRK6, LYPD3, EFNA4, and HER2; l) an antigen present on prostate cancer, wherein the antigen is optionally selected from PSMA, FOLH1, PTK7, STEAP, TMEFF2 (TENB2), OR51E2, SLC30A4, and EFNA4; m) an antigen present on thyroid cancer, wherein the antigen is optionally PTK7; n) an antigen present on uterine cancer, wherein the antigen is optionally selected from LY6K, PTK7, EPHB2, FOLR1, ALPPL2, MUC16, Nectin-4, and EFNA4; o) an antigen present on cervical/endometrial cancer, wherein the antigen is optionally selected from LY6K, PTK7, MUC16, LYPD3, EFNA4, Nectin4, and MUC1; and p) an antigen present on pancreatic cancer, wherein the antigen is optionally selected from PTK7, MUC16, MSLN, LRRC15, ADAM12, EFNA4, MUC5A, Nectin-4, and MUC1.

22. The method of any one of claims 1-21, wherein the antibody is an anti- HER2 antibody.

23. The method of any one of claims 1-22, wherein the antibody is pertuzumab, trastuzumab, or ladiratuzumab, or a biosimilar thereof; or comprises the CDRs of pertuzumab, trastuzumab, or ladiratuzumab; or comprises an antigen binding fragment of pertuzumab, trastuzumab, or ladiratuzumab.

24. The method of any one of claims 1-23, wherein the antibody comprises HC-CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

25. The method of any one of claims 1-24, wherein the method comprises administering an additional therapeutic agent.

26. The method of claim 25, wherein the additional therapeutic agent comprises a chemotherapy agent, a kinase inhibitor, a therapeutic antibody, or any combination thereof.

27. The method of claim 25 or 26, wherein the additional therapeutic agent comprises a therapeutic agent targeting HER2.

28. The method of any one of claims 25-27, wherein the additional therapeutic agent is selected from trastuzumab, trastuzumab-qyyp, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-anns, trastuzumab-dkst, trastuzumab, deruxtecan-nxki, ado-trastuzumab emtansine, trastuzumab duocarmazine, margetuximab, zenocutuzumab , tucatinib, cabozantinib, pyrotinib, and poziotinib.

29. The method of any one of claims 25-28, wherein the additional therapeutic agent comprises an anti-HER2 antibody, optionally wherein the therapeutic agent comprising the anti-HER2 antibody is selected from trastuzumab, trastuzumab- qyyp, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-anns, trastuzumab-dkst, trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, trastuzumab duocarmazine, margetuximab, and zenocutuzumab.

30. The method of claim 26, wherein the kinase inhibitor is a tyrosine kinase inhibitor or a serine/threonine kinase inhibitor.

31. The method of claim 30, wherein the kinase inhibitor is a tyrosine kinase inhibitor selected from tucatinib, cabozantinib, afatinib, erlotinib, pyrotinib, poziotinib, dacomitinib, gefitinib, lapatinib, osimertinib, larotrectinib, axitinib, lenvatinib, pazopanib, regorafenib, and sunitinib.

32. The method of claim 30, wherein the kinase inhibitor is a serine/threonine kinase inhibitor that is a CDK4/6 inhibitor selected from abemaciclib, palbociclib, and ribociclib.

33. The method of claim 26, wherein the chemotherapy agent comprises: (a) a hormone-based compound, optionally wherein the hormone based compound comprises anastrozole, exemestane, letrozole, fulvestrant, bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide, darolutamide, degarelix, toremifene, goserelin, triptorelin, histrelin, leuprolide, or tamoxifen citrate; (b) a platinum coordination complex, optionally wherein the platinum coordination complex comprises cisplatin, oxaliplatin, or carboplatin; (c) a folic acid analog, optionally wherein the folic acid analog comprises pemetrexed, methotrexate, or trimetrexate; (d) a pyrimidine analog, optionally wherein the pyrimidine analog comprises fluorouracil, capecitabine, fluorodeoxyuridine, tezacitabine, gemcitabine, cytosine arabinoside, cytarabine, 5-azacytidine, or 2,2ʹ-difluorodeoxycytidine; (e) a microtubule inhibitor, optionally wherein the microtubule inhibitor comprises paclitaxel, docetaxel, and eribulin; or any combination thereof.

34. The method of claim 25, wherein the additional therapeutic agent comprises a chemotherapy protective agent, optionally wherein the chemotherapy protective agent comprises leucovorin.

35. The method of any one of claims 1-4 and 6-34, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the immune checkpoint inhibitor is pembrolizumab; (c) optionally comprising an additional therapeutic agent, wherein the additional therapeutic agent comprises fam-trastuzumab deruxtecan-nxki or ado- trastuzumab emtansine; and (d) optionally, wherein the antibody comprises HC-CDR1, HC- CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

36. The method of claim 1-4 and 6-34, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the immune checkpoint inhibitor is nivolumab; (c) optionally, wherein the antibody comprises HC-CDR1, HC- CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

37. The method of any one of claims 25-29, and 33, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) optionally wherein the immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1 is pembrolizumab, nivolumab, or atezolizumab; (c) the additional therapeutic agent comprises: trastuzumab, a pyrimidine analog, optionally wherein the pyrmidine analog is fluorouracil or capecitabine, and a platinum coordination complex, optionally wherein the platinum coordination complex is oxaliplatin, or cisplatin; and (d) optionally wherein the cancer is gastric cancer; (e) optionally, wherein the antibody comprises HC-CDR1, HC- CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

38. The method of any one of claims 25-29, and 33, wherein: (a) L and Dx together have a structure selected from:

and salts thereof; (b) the immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1 is pembrolizumab, nivolumab, or atezolizumab; (c) the additional therapeutic agent comprises: (i) trastuzumab; and (ii) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); (c) optionally, wherein the cancer is gastric cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

39. The method of any one of claims 25-29, and 33, wherein: (a) L and Dx together have a structure selected from:

and salts thereof; (b) the immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1 is pembrolizumab, nivolumab, or atezolizumab; (c) the additional therapeutic agent comprises: (i) trastuzumab; (ii) leucovorin, (iii) fluorouracil; and (iv) cisplatin; (d) optionally, wherein the cancer is gastric cancer; and (e) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

40. The method of any one of claims 25-29, and 33, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1 is pembrolizumab, nivolumab, or atezolizumab; (c) the additional therapeutic agent comprises: (i) trastuzumab; (ii) capecitabine; (iii) oxaliplatin; and (c) optionally, wherein the cancer is gastric cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

41. The method of any one of claims 25-29 and 33, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1 is pembrolizumab, nivolumab, or atezolizumab; (c) the additional therapeutic agent comprises: (i) trastuzumab; and (ii) optionally capecitabine; (d) optionally, wherein the cancer is gastric cancer; and (e) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

42. The method of any one of claims 25-29 and 33, wherein: (a) L and Dx together have a structure selected from:

and salts thereof; (b) the immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1 comprises pembrolizumab, and optionally atezolizumab; (c) the additional therapeutic agent comprises: (i) trastuzumab; and (ii) docetaxel or paclitaxel; (d) optionally, wherein the cancer is breast cancer; and (e) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

43. The method of any one of claims 25-29 and 33, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the immune checkpoint inhibitor that inhibits PD-1 and/or PD-L1 is atezolizumab or durvalumab; (c) the additional therapeutic agent comprises fam-trastuzumab deruxtecan-nxki or ado-trastuzumab emtansine; (d) optionally wherein the cancer is breast cancer; and (e) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

44. The method of any one of claims 25, 26, and 33, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the immune checkpoint inhibitor is pembrolizumab; (c) the additional therapeutic agent comprises: (i) pemetrexed; and (ii) carboplatin or cisplatin; (c) optionally, wherein the cancer is non-small cell lung cancer; and/or (d) optionally, wherein the antibody comprises HC-CDR1, HC- CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

45. The method of any one of claims 25, 26, and 33, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the immune checkpoint inhibitor is atezolizumab; (c) the additional therapeutic agent comprises: (i) paclitaxel; (ii) carboplatin; and (iii) bevacizumab; (c) optionally, wherein the cancer is non-small cell lung cancer; and/or (d) optionally, wherein the antibody comprises HC-CDR1, HC- CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

46. The method of claim 25-29, wherein the conjugate comprises pertuzumab or a biosimilar thereof, or comprises the CDRs of pertuzumab, or comprises an antigen binding fragment of pertuzumab, and the additional therapeutic agent comprises trastuzumab or comprises the CDRs of trastuzumab, or comprises an antigen binding fragment of trastuzumab.

47. The method of any one of claims 1-46, wherein the cancer expresses HER2 at a level of 2+ or 3+ as determined by immunohistochemistry.

48. The method of claim 47, wherein the cancer expresses HER2 at a level of 3+ as determined by immunohistochemistry.

49. The method of any one of claims 1-48, wherein the antibody of the conjugate comprises an antigen binding domain and an Fc domain.

50. The method of claim 49, wherein the Fc domain exhibits the same or substantially similar binding affinity to at least one Fcgamma receptor and/or an FcRn receptor as compared to a wild-type IgG1 Fc domain.

51. The method of claim 49, wherein the Fc domain has increased binding affinity to at least one Fcgamma receptor as compared to a wild-type IgG Fc domain.

52. The method of any one of claims 49-51, wherein the Fc domain is an IgG1 Fc domain.

53. The method of any one of claims 1-52, wherein the method comprises administering an effective regimen of the conjugate, wherein the effective regimen results in a Tmax of the conjugate in the subject of greater than 4 hours following each administration of the conjugate.

54. The method of any one of claims 1-53, wherein the method comprises administering an effective regimen of the conjugate, wherein the effective regimen comprises at least two cycles of administration of the conjugate to the subject and a total dose of greater than 0.4 mg/kg of the conjugate per cycle.

55. The method of any one of claims 1-54, wherein the conjugate is administered subcutaneously.

56. The method of any one of claims 1-54, wherein the conjugate is administered intravenously.

57. A method of treating a HER2-expressing cancer, comprising administering to a subject with a HER2-expressing cancer a conjugate and an additional therapeutic agent comprising a kinase inhibitor, a therapeutic agent comprising an anti- HER2 antibody, or both; wherein the conjugate is represented by Formula (I):

wherein: A is an antibody that binds HER2, L is a linker; D_x is a TLR8 agonist, wherein the TLR8 agonist is a benzazepine compound; n is selected from 1 to 20; and z is selected from 1 to 20.

58. The method of claim 57, wherein n is 1 and z is from 1 to 8.

59. The method of claim 57 or claim 58, wherein the antibody of the conjugate is pertuzumab or trastuzumab, or a biosimilar thereof; or comprises the CDRs of pertuzumab or trastuzumab; or comprises an antigen binding fragment of pertuzumab or trastuzumab.

60. The method of any one of claims 57-59, wherein the antibody of the conjugate comprises HC-CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

61. The method of any one of claims 57-60, wherein the additional therapeutic agent comprises an anti-HER2 antibody that binds to a different epitope as compared to the conjugate antibody that binds HER2.

62. The method of any one of claims 57-61, wherein the additional therapeutic agent is selected from trastuzumab, trastuzumab-qyyp, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-anns, trastuzumab-dkst, trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, trastuzumab duocarmazine, margetuximab, zenocutuzumab , tucatinib, cabozantinib, pyrotinib, and poziotinib.

63. The method of any one of claims 57-60, wherein the kinase inhibitor is a tyrosine kinase inhibitor, optionally wherein the tyrosine kinase inhibitor is tucatinib, cabozantinib, afatinib, erlotinib, pyrotinib, poziotinib, dacomitinib, gefitinib, lapatinib, osimertinib, larotrectinib, axitinib, lenvatinib, pazopanib, regorafenib, or sunitinib.

64. The method of any one of claims 57-60, wherein the kinase inhibitor is a CDK4/6 kinase inhibitor, optionally wherein the CDK4/6 kinase inhibitor is palbociclib, abemaciclib, or ribociclib.

65. The method of any one of claims 57-64, the additional therapeutic agent further comprises a chemotherapy agent, an immune checkpoint inhibitor, chemotherapy protective agent, or any combination thereof.

66. The method of any one of claims 57-65, wherein the conjugate comprises pertuzumab or comprises the CDRs of pertuzumab, or comprises an antigen binding fragment of pertuzumab; and the additional therapeutic agent comprises trastuzumab, or a biosimilar thereof, or comprises the CDRs or trastuzumab; or comprises an antigen binding fragment of trastuzumab.

67. The method of any one of claims 57-66, wherein the cancer expresses HER2 at a level of 2+ or 3+ as determined by immunohistochemistry.

68. The method of claim 67, wherein the cancer expresses HER2 at a level of 3+ as determined by immunohistochemistry.

69. The method of any one of claims 57-68, wherein the TLR8 agonist is a compound of Category A, Formula (IIB):

or a pharmaceutically acceptable salt thereof, wherein: L¹⁰ is -X¹⁰-; L² is selected from -X²-, -X²-C_1-6 alkylene-X²-, -X²-C_2-6 alkenylene-X²-, and -X²-C_2-6 alkynylene-X²-, each of which is optionally substituted on alkylene, alkenylene or alkynylene with one or more R¹²; X¹⁰ is selected from -C(O)-, and -C(O)N(R¹⁰)-*, wherein * represents where X¹⁰ is bound to R⁵; X² at each occurrence is independently selected from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, -C(O)N(R¹⁰)C(O)N(R¹⁰), -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-, -S(O)₂-, -OS(O)-, -S(O)O-, -S(O), -OS(O)₂-, -S(O)₂O, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from hydrogen; and C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R⁴ is selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R⁵ is selected from unsaturated C_4-8 carbocycle; bicyclic carbocycle; and fused 5-5, fused 5-6, and fused 6-6 bicyclic heterocycle, wherein R⁵ is optionally substituted and wherein substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁵ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁰ is independently selected at each occurrence from hydrogen, -NH₂, -C(O)OCH2C6H5; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C_3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl; wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle; R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴ and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C_3-7 carbocycle.

70. The method of any one of claims 57-69, wherein the TLR8 agonist is a compound of Category A, Formula IIC:

or a pharmaceutically acceptable salt thereof, wherein: R¹ and R² are hydrogen; L² is -C(O)-; R⁴ is -N(R¹⁰)₂; R¹⁰ is independently selected at each occurrence from hydrogen, -NH2, -C(O)OCH2C6H5; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C_1-10 alkyl, -C_1-10 haloalkyl, -O-C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L¹⁰ is -C(O)N(R¹⁰)-*, wherein * represents where L¹⁰ is bound to R⁵; and R⁵ is a fused 5-5, fused 5-6, or fused 6-6 bicyclic heterocycle, wherein R⁵ is optionally substituted and wherein substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl.

71. The method of claim 70, wherein R⁴ is -N(C_1-4 alkyl)₂ and L¹⁰ is -C(O)N(H)-*.

72. The method of claim 70 or 71, wherein:

.

73. The method of any one of claims 57-72, wherein the TLR8 agonist is selected from:

pharmaceutically acceptable salts thereof.

74. The method of any one of claims 57-73, wherein Dx is a compound of Formula (IVB):

or a pharmaceutically acceptable salt thereof, wherein: L¹² is selected from -X³-, -X³-C_1-6 alkylene-X³-, -X³-C_2-6 alkenylene-X³-, and - X³-C_2-6 alkynylene-X³-, each of which is optionally substituted on alkylene, alkenylene, or alkynylene with one or more substituents independently selected from R¹²; L²² is independently selected from -X⁴-, -X⁴-C1-6 alkylene-X⁴-, -X⁴-C_2-6 alkenylene-X⁴-, and -X⁴-C_2-6 alkynylene-X⁴-, each of which is optionally substituted on alkylene, alkenylene, or alkynylene with one or more substituents independently selected from R¹⁰; X³ and X⁴ are independently selected at each occurrence from a bond, -O-, -S-, -N(R¹⁰)-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -C(O)N(R¹⁰)-, -C(O)N(R¹⁰)C(O)-, -C(O)N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)-, -N(R¹⁰)C(O)N(R¹⁰)-, -N(R¹⁰)C(O)O-, -OC(O)N(R¹⁰)-, -C(NR¹⁰)-, -N(R¹⁰)C(NR¹⁰)-, -C(NR¹⁰)N(R¹⁰)-, -N(R¹⁰)C(NR¹⁰)N(R¹⁰)-, -S(O)₂-, -OS(O)-, -S(O)O-, -S(O)-, -OS(O)₂-, -S(O)₂O-, -N(R¹⁰)S(O)₂-, -S(O)₂N(R¹⁰)-, -N(R¹⁰)S(O)-, -S(O)N(R¹⁰)-, -N(R¹⁰)S(O)₂N(R¹⁰)-, and -N(R¹⁰)S(O)N(R¹⁰)-; R¹ and R² are independently selected from L³, and hydrogen; and C_1-10 alkyl, C_2- 10 alkenyl, and C_2-10 alkynyl, each of which is optionally bound to L³ and each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; R⁴ and R⁸ are independently selected from: -OR¹⁰, -N(R¹⁰)₂, -C(O)N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -S(O)R¹⁰, and -S(O)₂R¹⁰; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally bound to L³ and each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12-membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, wherein each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ and R⁸ is optionally bound to L³ and each C_3-12 carbocycle, and 3- to 12-membered heterocycle in R⁴ and R⁸ is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl; R¹⁰ is independently selected at each occurrence from L³, hydrogen, -NH₂, -C(O)OCH2C6H5; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L³ is a linker moiety, wherein there is at least one occurrence of L³; and R¹² is independently selected at each occurrence from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C3-10 carbocycle and 3- to 10-membered heterocycle; and C_3-10 carbocycle and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle in R¹² is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰ _, -C(O)OR¹⁰, -OC(O)R¹⁰, -S(O)R¹⁰, -S(O)₂R¹⁰, -P(O)(OR¹⁰)₂, -OP(O)(OR¹⁰)₂, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl; wherein any substitutable carbon on the benzazepine core is optionally substituted by a substituent independently selected from R¹² or two substituents on a single carbon atom combine to form a 3- to 7- membered carbocycle; R²⁰, R²¹, R²², and R²³ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; and R²⁴, and R²⁵ are independently selected from hydrogen, halogen, -OR¹⁰, -SR¹⁰, -N(R¹⁰)₂, -S(O)R¹⁰, -S(O)₂R¹⁰, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-10 alkyl, C_2-10 alkenyl, and C_2-10 alkynyl; or R²⁴ and R²⁵ taken together form an optionally substituted saturated C_3-7 carbocycle.

75. The method of any one of claims 57-74, wherein Dx is a compound of Formula (IVC):

or a pharmaceutically acceptable salt thereof, wherein: R¹ and R² are hydrogen; L²² is -C(O)- R⁴ is -N(R¹⁰)₂; R¹⁰ is independently selected at each occurrence from hydrogen, -NH₂, -C(O)OCH2C6H5; and C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -CN, -NO₂, -NH2, =O, =S, -C(O)OCH₂C₆H₅, -NHC(O)OCH₂C₆H₅, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, C_3-12 carbocycle, 3- to 12-membered heterocycle, and haloalkyl; L¹² is -C(O)N(R¹⁰)-*, wherein * represents where L¹² is bound to R⁸; R⁸ is an optionally substituted fused 5-5, fused 5-6, or fused 6-6 bicyclic heterocycle bound to linker moiety L³ , and wherein optional substituents are independently selected at each occurrence from: halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), and -CN; C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO2, =O, =S, =N(R¹⁰), -CN, C_3-12 carbocycle, and 3- to 12- membered heterocycle; and C_3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR¹⁰, -SR¹⁰, -C(O)N(R¹⁰)₂, -N(R¹⁰)C(O)R¹⁰, -N(R¹⁰)C(O)N(R¹⁰)₂, -N(R¹⁰)₂, -C(O)R¹⁰, -C(O)OR¹⁰, -OC(O)R¹⁰, -NO₂, =O, =S, =N(R¹⁰), -CN, C_1-6 alkyl, C_2-6 alkenyl, and C_2-6 alkynyl.

76. The method of claim 75, wherein R⁴ is -N(C1-4 alkyl)₂ and L¹² is -C(O)N(H)-*.

77. The method of claim 75 or 76, wherein:

.

78. The method of any one of claims 57-77, wherein L and Dx together have a structure selected from:

, and salts thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein

on RX* represents the point of attachment to the residue of the antibody.

79. The method of claim 78, wherein L and Dx together have a structure selected from:

, and salts thereof, wherein the RX^* is a bond, a succinimide moiety, or a hydrolyzed succinimide moiety bound to a residue of an antibody, wherein on RX* represents the point of attachment to the residue of the antibody.

80. The compound or salt of claim 78 or 79, wherein RX* comprises a succinamide moiety and is bound to a cysteine residue of the antibody.

81. The compound or salt of claim 78 or 79, wherein RX* comprises a hydrolyzed succinamide moiety and is bound to a cysteine residue of the antibody.

82. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

(b) the additional therapeutic agent comprises trastuzumab; and (c) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

83. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

(b) the additional therapeutic agent comprises fam-trastuzumab deruxtecan-nxki; and (c) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

84. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

(b) the additional therapeutic agent comprises ado-trastuzumab emtansine; and (c) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

85. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises tucatinib; and (c) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

86. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises palbociclib, abemaciclib, or ribociclib; (c) optionally wherein the HER2-expressing cancer is breast cancer; and (d) optionally, wherein the antibody comprises HC-CDR1, HC- CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

87. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from:

and salts thereof; (b) the additional therapeutic agent comprises: (i) trastuzumab; (ii) a pyrimidine analog, optionally wherein the pyrimidine analog is fluorouracil or capecitabine; (iii) a platinum coordination complex, optionally wherein the platinum coordination complex is oxaliplatin, or cisplatin; (iii) a PD-1 and/or PD-L1 inhibitor, optionally wherein the PD-1 and/or PD-L1 inhibitor is pembrolizumab, nivolumab, or atezolizumab; (c) optionally wherein the HER2-expressing cancer is gastric cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

88. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises: (i) trastuzumab; (ii) a chemotherapy regimen comprising leucovorin, fluorouracil, and oxaliplatin (FOLFOX); and (iii) optionally pembrolizumab, nivolumab, or atezolizumab; (c) optionally wherein the HER2-expressing cancer is gastric cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

89. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises: (i) trastuzumab; (ii) leucovorin, (iii) fluorouracil; (iv) cisplatin; and (iii) optionally pembrolizumab, nivolumab, or atezolizumab; (c) optionally, wherein the HER2-expressing cancer is gastric cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

90. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises: (i) trastuzumab; (ii) capecitabine; (iii) oxaliplatin; and (iv) optionally pembrolizumab, nivolumab, or atezolizumab; (c) optionally, wherein the HER2-expressing cancer is gastric cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

91. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises: (i) trastuzumab; (ii) pembrolizumab, nivolumab, or atezolizumab; and (iii) optionally capecitabine; (c) optionally, wherein the HER2-expressing cancer is gastric cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

92. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises: (i) trastuzumab; (ii) pembrolizumab; (iii) docetaxel or paclitaxel; and (iv) optionally, atezolizumab; (c) optionally, wherein the HER2-expressing cancer is breast cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

93. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from:

and salts thereof; (b) the additional therapeutic agent comprises one of the following combinations: (i) fam-trastuzumab deruxtecan-nxki and durvalumab, (ii) fam-trastuzumab deruxtecan-nxki and atezolizumab, (iii) ado-trastuzumab emtansine and durvalumab; and (iv) ado-trastuzumab emtansine and atezolizumab; (c) optionally wherein the HER2-expressing cancer is breast cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

94. The method of any one of claims 57-81, wherein: (a) L and Dx together have a structure selected from: ,

and salts thereof; (b) the additional therapeutic agent comprises: (i) trastuzumab; (ii) a hormone-based compound; and (ii) palbociclib or abemaciclib; (c) optionally, wherein the HER2-expressing cancer is breast cancer; and (d) optionally, wherein the antibody of the conjugate comprises HC- CDR1, HC-CDR2, HC-CDR3, LC-CDR1, LC-CDR2, and LC-CDR3 of SEQ ID NOs: 1-6, respectively; or the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; or the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

95. The method of any one of claims 57-94, wherein the antibody of the conjugate comprises an antigen binding domain and an Fc domain.

96. The method of claim 95, wherein the Fc domain exhibits the same or substantially similar binding affinity to at least one Fcgamma receptor and/or an FcRn receptor as compared to a wild-type IgG1 Fc domain.

97. The method of claim 95, wherein the Fc domain has increased binding affinity to at least one Fcgamma receptor as compared to a wild-type IgG Fc domain.

98. The method of any one of claims 95-97, wherein the Fc domain is an IgG1 Fc domain.

99. The method of any one of claims 57-98, wherein the method comprises administering an effective regimen of the conjugate, wherein the effective regimen results in a Tmax of the conjugate in the subject of greater than 4 hours following each administration of the conjugate.

100. The method of any one of claims 57-99, wherein the method comprises administering an effective regimen of the conjugate, wherein the effective regimen comprises at least two cycles of administration of the conjugate to the subject and a total dose of greater than 0.4 mg/kg of the conjugate per cycle.

101. The method of any one of claims 57-100, wherein the conjugate is administered subcutaneously.

102. The method of any one of claims 57-100, wherein the conjugate is administered intravenously.

103. The method of any one of claims 57-102, wherein the HER2-expressing cancer is selected from breast cancer, stomach/gastric cancer, colorectal cancer, non- small cell lung cancer (NSCLC), urothelial cancer, endometrial cancer, and ovarian cancer.