EP4676967A1

EP4676967A1 - Anti-cd276 and anti-cd99 logic gated chimeric antigen receptors for the treatment of cancer

Info

Publication number: EP4676967A1
Application number: EP24717494.9A
Authority: EP
Inventors: Sujatha VENKATARAMAN; Mark Eric KOHLER; Rajeev Vibhakar
Original assignee: University of Colorado System; University of Colorado Colorado Springs; University of Colorado Denver
Current assignee: University of Colorado System; University of Colorado Colorado Springs; University of Colorado Denver
Priority date: 2023-03-10
Filing date: 2024-03-11
Publication date: 2026-01-14
Also published as: AU2024236108A1; JP2026509363A; WO2024191918A1

Abstract

The present disclosure provides compositions and methods directed to logic gated CAR-T therapies for treating cancer, such as DIPG, Ewing Sarcoma, and AML, including logic pairs of CAR polypeptides comprising anti-CD276 CAR polypeptides and anti-CD99 CAR polypeptides.

Description

Attorney Docket No.: UNCO-064/001WO 300978-2237 ANTI-CD276 AND ANTI-CD99 LOGIC GATED CHIMERIC ANTIGEN RECEPTORS FOR THE TREATMENT OF CANCER RELATED APPLICATIONS [0001] This application claims priority to, and the benefit of, U.S. Provisional Application No.63/489,724, filed on March 10, 2023, the contents of which is incorporated herein by reference in its entirety. GOVERNMENT SUPPORT [0002] This invention was made with government support under K12 CA086913-18 awarded by the National Cancer Institute. The government has certain rights in the invention. SEQUENCE LISTING [0003] The Sequence Listing XML associated with this application is provided electronically in XML file format and is hereby incorporated by reference into the specification. The name of the XML file containing the Sequence Listing XML is “UNCO-064_001WO_SeqList”. The XML file is 87,472 bytes, created on March 10, 2024, and is being submitted electronically via USPTO Patent Center. BACKGROUND [0004] Diffuse intrinsic pontine glioma (DIPGs) is the most aggressive pediatric brain tumor and the leading cause of brain tumor-related death in children. DIPG diffusely involves the pons, making it inoperable and resulting in a median survival of 11 months for children with this tumor. Radiation therapy provides only temporary relief and chemotherapy is not effective. For the same reasons, the 5-year survival rate has held steady at 0% since 1950. Recent studies have shown that a somatic Lys27Met substitution in histone 3.3 (H3.3K27M mutation) occurs in more than 85% of patients with DIPG and is associated with poor survival. While these studies give crucial insight into driver mutations they have not yet resulted in new therapeutic options. Thus, there is a critical need to identify and validate more effective, biologically based therapies to target DIPG, including DIPG that specifically arises from the presence of H3K27M mutation. [0005] Recently, Chimeric Antigen Receptor (CAR) T cells targeting DIPG have shown promise in preclinical models and are in development for clinical trials. However, a major obstacle in the use of CAR T cell therapy for treatment of solid tumors (e.g. DIPG) is the Attorney Docket No.: UNCO-064/001WO 300978-2237 absence of true "tumor only" antigens. Most target antigens are also expressed by multiple normal cells – creating the risk of targeting normal cells in addition to cancer cells. In the context of DIPG, single-antigen targeting CAR-T cells have limited effectiveness due to off- target toxicity and low antigen densities on the tumor, which may lead to tumor escape. For example, preliminary data has demonstrated that CD56 CAR-T cells effectively target DIPG cells but cause neurotoxicity in mice due to cross-reactivity on normal brain cells. Moreover, CD99 CAR-T cells initially demonstrate complete clearance of tumor burden in DIPG xenograft models, but tumor recurrence may occur. Without wishing to be limited by theory, recurrences likely due to loss of the CAR-T cells as they also express the target antigen, CD99 (i.e. cellular fratricide). Accordingly, there is a need in the art for improved CAR-T cell treatments for DIPG. The present disclosure addresses this need by providing “logic pairs” of CAR polypeptides (and associated methods and compositions) for use in the treatment of various cancers, including DIPG. [0006] In addition to DIPG, the logic pairs of CAR polypeptides of the present disclosure, as well as their associated methods and compositions, can also be used in the treatment of other cancers such as acute myeloid leukemia (AML), Ewing’s sarcoma, posterior fossa type A (PFA) ependymoma, and atypical teratoid rhabdoid tumors (ATRT). [0007] AML is a blood cancer in which the bone marrow of a subject makes abnormal myeloblasts, red blood cells, or platelets. AML is one of the most common forms of acute leukemia in adults. The build-up of AML cells in bone marrow and blood can rapidly lead to infection, anemia, excessive bleeding and death. BCL-2 inhibitor venetoclax has recently emerged as an important component of therapy for acute myeloid leukemia (AML). The current FDA-approved standard of care for the majority of patients who are too elderly or unfit for aggressive chemotherapy is treatment with venetoclax in combination with a hypomethylating agent, such as azacitidine (“Ven/aza treatment”) or decitabine. It is estimated that approximately 70% of these patients will achieve complete remission (CR) of their disease upon Ven/aza treatment. However, it is estimated that approximately 30% of patients do not respond to treatment with ven/aza and are unable to achieve CR. Accordingly, there is an unmet need in the art for improved compositions and methods for treating AML, including in subjects that will not respond to treatment with Ven/aza. [0008] Ewing sarcoma is a type of cancer that occurs primarily in the bone or soft tissue. While Ewing sarcoma can develop in any bone, it is most often found in the hip bones, ribs, or long bones (e.g., femur, tibia or humerus). It can involve the muscle and the soft tissues around the tumor as well. Ewing sarcoma cells can also metastasize (spread) to other areas of Attorney Docket No.: UNCO-064/001WO 300978-2237 the body, including the bone marrow, lungs, kidneys, heart, adrenal glands and other soft tissues. As the second-most common type of bone cancer affecting children and young adults, it accounts for about 1 percent of childhood cancers. About 225 children and adolescents are diagnosed with Ewing sarcoma in the U.S. each year. While Ewing sarcoma can occur at any time during childhood, it most commonly develops during puberty, when bones are growing rapidly. Ewing sarcoma most often occurs in children between the ages of 10 and 20. Over the last 40 years, both local therapy and multiagent adjuvant chemotherapy have achieved considerable progress in the treatment of localized disease that improved the 5-year survival rate from less than 20% to greater than 70%, but the recurrence rate remains high. However, most present locally, and subclinical metastatic disease is present in almost all cases. Approximately 25% of patients with initially localized disease ultimately relapse. No standard therapy exists for relapsed and refractory Ewing sarcoma, with survival rates being less than 30% in those with isolated lung metastases and less than 20% in those with bone and bone marrow involvement. Accordingly, there is an unmet need in the art for improved compositions and methods for treating Ewing’s sarcoma, including in subjects with relapsed and refractory disease. SUMMARY [0009] The present disclosure provides pairs of chimeric antigen receptor (CAR) polypeptides comprising an anti-CD276 CAR polypeptide and an anti-CD99 CAR polypeptide, wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C- terminus, i) a signal peptide; ii) an anti-CD276 antigen binding domain comprising an anti- CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; iii) a hinge domain comprising a CD28 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 40; iv) a transmembrane domain comprising a CD28 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 44; v) a costimulatory domain comprising a CD28 costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 48; and wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising the anti-CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation polypeptide comprising the amino acid sequence of SEQ ID NO: 52. In some aspects, the Attorney Docket No.: UNCO-064/001WO 300978-2237 anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 63, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 65. [0010] The present disclosure provides pairs of CAR polypeptides comprising an anti- CD276 CAR polypeptide and an anti-CD99 CAR polypeptide, wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD276 antigen binding domain comprising an anti-CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; v) a costimulatory domain comprising a 4-1BB costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 50; and wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising the anti-CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation polypeptide comprising the amino acid sequence of SEQ ID NO: 52. In some aspects, the anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 64, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 65. [0011] The present disclosure provides pairs of chimeric antigen receptor (CAR) polypeptides comprising an anti-CD276 CAR polypeptide and an anti-CD99 CAR polypeptide, wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C- terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising an anti- CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD28 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 40; iv) a transmembrane domain comprising a CD28 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 44; v) a costimulatory domain comprising a CD28 costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 48; and wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD276 antigen binding domain comprising the anti-CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation Attorney Docket No.: UNCO-064/001WO 300978-2237 polypeptide comprising the amino acid sequence of SEQ ID NO: 52. In some aspects, the anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 61, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 62. [0012] The present disclosure provides pairs of CAR polypeptides comprising an anti-CD276 CAR polypeptide and an anti-CD99 CAR polypeptide, wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising an anti-CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; v) a costimulatory domain comprising a 4-1BB costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 50; and wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD276 antigen binding domain comprising the anti-CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation polypeptide comprising the amino acid sequence of SEQ ID NO: 52. In some aspects, the anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 60, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 62. [0013] The present disclosure provides nucleic acid molecules comprising: at least nucleic acid sequence encoding for an anti-CD276 CAR polypeptide of a pair of CAR polypeptides of the present disclosure; and at least nucleic acid sequence encoding for an anti-CD99 CAR polypeptide of a pair of CAR polypeptides of the present disclosure. In some aspects, the at least one nucleic acid sequence encoding for the anti-CD276 CAR polypeptide and the at least one nucleic acid sequence encoding for the anti-CD99 CAR polypeptide are separated by at least one nucleic acid sequence that encodes a self-cleaving peptide. In some aspects, a self-cleaving peptide is the P2A self-cleaving peptide. [0014] The present disclosure provides vectors comprising the nucleic acid molecules of the present disclosure. In some aspects, a vector is a viral vector. In some aspects, a viral vector is an AAV vector or a lentiviral vector. [0015] The present disclosure provide cells expressing the pair of CAR polypeptides of the present disclosure. In some aspects the cell is an immune cell. In some aspects, the immune Attorney Docket No.: UNCO-064/001WO 300978-2237 cell is a T cell, NK cell, NK-like cell, NKT cell, or cytokine induced killer (CIK) cell. In some aspects, the immune cell is a T cell. [0016] The present disclosure provides populations of cells of the present disclosure. [0017] The present disclosure provides methods of treating cancer in a subject, the methods comprising administering to the subject one or more amounts of the cell populations of the present disclosure. [0018] The present disclosure provides methods of preventing cancer metastasis in a subject, the method comprising administering one or more amounts of the cell populations of the present disclosure. [0019] In some aspects, the methods further comprise administering to the subject at least one additional therapy. In some aspects, the at least one additional therapy comprises at least one of radiation therapy, chemotherapy, and surgery. [0020] In some aspects, the cancer is diffuse intrinsic pontine glioma (DIPG), acute myeloid leukemia (AML), Ewing sarcoma, posterior fossa type A (PFA) ependymoma, or an atypical teratoid rhabdoid tumor (ATRT). [0021] Any of the above aspects, or any aspect herein, can be combined with any other aspect. [0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the Specification, the singular forms also include the plural unless the context clearly dictates otherwise; as examples, the terms “a,” “an,” and “the” are understood to be singular or plural and the term “or” is understood to be inclusive. By way of example, “an element” means one or more element. Throughout the specification the word “comprising,” or variations such as “comprises” or “comprising,” will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. About can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from the context, all numerical values provided herein are modified by the term “about.” [0023] Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present Attorney Docket No.: UNCO-064/001WO 300978-2237 Specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Other features and advantages of the disclosure will be apparent from the following detailed description and claim. BRIEF DESCRIPTION OF THE DRAWINGS [0024] The above and further features will be more clearly appreciated from the following detailed description when taken in conjunction with the accompanying drawings. [0025] FIGs.1A-1B show the engineering of dual-antigen CARs. FIG.1A shows a schematic of a CAR designed so that only binding to both antigens on the same cell will lead to full activation of the CAR. FIG.1B shows two logic gated CAR constructs. [0026] FIG.2 and FIG.3 show CD99/CD276 logic gated CAR constructs protect single- antigen T cells and inhibit T cell fratricide. FIG.2 shows ELISA measurements of cytokine production in T cells expressing only CD99 after treatment with mock CAR-T cells, single antigen CD99-BBz CAR-T cells, single antigen CD276-BBz CAR-T cells, or either of the CD99/CD276 logic gated CAR-T cells. FIG.3 shows percentage viability of CD99 expressing CAR-T cells over time after transduction with respective CAR constructs. [0027] FIGs.4A-4C show the functionality of single antigen CAR-T cell therapy against DIPG. FIG.4A shows XCELLigence real-time cell proliferation measurements of DIPG007 tumor cells treated with single antigen CD99 CAR-T cells and single antigen CD276 CAR-T cells compared to DIPG007 tumor cells treated with single antigen CD19 CAR-T cells. FIG. 4B shows ELISA measurements of cytokine production in DIPG007 cells after treatment with single antigen CD19 CAR-T cells, single antigen CD99 CAR-T cells, or single antigen CD276 CAR-T cells. FIG.4C shows ELISA measurements of cytokine production in DIPG BT245 cells after treatment with singe antigen CD19 CAR-T cells or single antigen CD99 CAR-T cells. [0028] FIGs.5A-5C show the functionality of CD99/CD276 logic gated CAR-T cells against DIPG in vitro. FIG.5A shows XCELLigence real-time cell proliferation measurements of DIPG007 tumor cells treated CD99/CD276 logic gated CAR-T cells compared to DIPG007 tumor cells treated with single antigen CD19 CAR-T cells. FIG.5B shows ELISA measurements of cytokine production in DIPG007 cells after treatment with single antigen CD19 CAR-T cells or CD99/ CD276 logic gated CAR-T cells. FIG.5C shows CAR-T cell death as measured by an increase in caspase 3/7 incucyte reagent when co-cultured with RAJI cells expressing CD99 only. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0029] FIGs.6A-6B shows the functionality of CD99/CD276 logic gated CAR-T cells against DIPG in vivo. FIG.6A shows Kaplan Meier’s survival analysis of the BT245 pons- bearing DIPG tumor mouse model post single-dose systemic infusion of single antigen CD19 CAR-T cells, single antigen CD99 CAR-T cells, single antigen CD276 CAR-T cells, or CD99/CD276 logic gated CAR-T cells. FIG.6B shows Kaplan Meier’s survival analysis of the DIPG007 pons-bearing DIPG tumor mouse model post single dose systemic infusion of single antigen CD19 CAR-T cells, single antigen CD99 CAR-T cells, single antigen CD276 CAR-T cells, or CD99/CD276 logic gated CAR-T cells. [0030] FIG.7 and FIG.8 show the functionality of CD99/CD276 logic gated CAR-T cells against PFA EPN in vitro. FIG.7 shows XCELLigence real-time cell proliferation measurements of PFN EPN MAF928 cells treated CD99/CD276 logic gated CAR-T cells compared to PFN EPN MAF928 tumor cells treated with single antigen CD19 CAR-T cells (mock). FIG.8 shows ELISA measurements of cytokine production in PFN EPN MAF928 cells after treatment with single antigen CD19 CAR-T cells or CD99/ CD276 logic gated CAR-T cells. [0031] FIG.9 shows Kaplan Meier’s survival analysis of the ATRT tumor mouse model post single dose systemic infusion of single antigen CD19 CAR-T cells or CD99/CD276 logic gated CAR-T cells. [0032] FIG.10 shows the functionality of CD99/CD276 logic gated CAR-T cells against Ewing Sarcoma in vivo. FIG.10 shows Kaplan Meier’s survival analysis of the Ewing Sarcoma tumor mouse model post single dose infusion of single antigen CD19 CAR-T cells, single antigen CD99 CAR-T cells, single antigen CD276 CAR-T cells, or CD99/CD276 logic gated CAR-T cells. [0033] FIG.11 show the anti-tumor efficacy of CD99/CD276 logic gated CAR-T cells against CD276-low expressing K562 cells. FIG.11 shows tumor volume measured with a caliper over time after CAR-T cell infusion. DETAILED DESCRIPTION [0034] Anti-CD276 CAR polypeptides [0035] The present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, an anti-CD276 antigen binding domain, a transmembrane domain and at least one costimulatory domain. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0036] The present disclosure also provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, an anti-CD276 antigen binding domain, a transmembrane domain and an activation domain. [0037] In some aspects, the anti-CD276 CAR polypeptides of the present disclosure can further comprise a hinge domain located between the anti-CD276 antigen binding domain and the transmembrane domain. Accordingly, the present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, an anti-CD276 antigen binding domain, a hinge domain, a transmembrane domain and at least one costimulatory domain. The present disclosure also provides anti- CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N- terminus to C-terminus, an anti-CD276 antigen binding domain, a hinge domain, a transmembrane domain and an activation domain. [0038] In some aspects, the anti-CD276 CAR polypeptides of the present disclosure can further comprise a signal peptide at the N-terminus of the anti-CD276 CAR polypeptide. Accordingly, the present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain, a transmembrane domain and at least one costimulatory domain. The present disclosure also provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain, a transmembrane domain and an activation domain. As described supra, the anti-CD276 CAR polypeptides of the present disclosure can also comprise a hinge domain. Accordingly, the present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C- terminus, a signal peptide, an anti-CD276 antigen binding domain, a hinge domain, a transmembrane domain and at least one costimulatory domain. The present disclosure also provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain, a hinge domain, a transmembrane domain and an activation domain. [0039] The anti-CD276 antigen binding domains, the transmembrane domains, the costimulatory domains, the signal peptides, the hinge domains, and the activation domains of the anti-CD276 CAR polypeptides of the present disclosure can be selected from any of the anti-CD276 antigen binding domains, the transmembrane domains, the costimulatory domains, the signal peptides, the hinge domains, and the activation domains of the anti- CD276 CAR polypeptides described in further detail herein. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0040] The following are exemplary anti-CD276 CAR polypeptides of the present disclosure. [0041] The present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and an activation domain comprising a CD3ȗ activation polypeptide. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide. [0042] The present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, wherein the anti- CD276 scFv comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 12, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises an amino acid sequence that is at least 97%, 98%, 99% identical to SEQ ID NO: 46, and an activation domain comprising a CD3ȗ activation polypeptide, wherein the CD3ȗ activation polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 52. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide, wherein the GMCSF signal peptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 58. [0043] The present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, wherein the anti- CD276 scFv comprises the amino acid sequence of SEQ ID NO: 12, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises the amino acid sequence of SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises the amino acid sequence of SEQ ID NO: 46, and an activation domain comprising a CD3ȗ activation polypeptide, wherein the CD3ȗ activation polypeptide comprises the amino acid sequence of SEQ ID NO: 52. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide, wherein the GMCSF signal peptide comprises the amino acid sequence of SEQ ID NO: 58. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0044] In some aspects, a an anti-CD276 CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 62. [0045] The present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, a hinge domain comprising a CD28 hinge polypeptide, a transmembrane domain comprising a CD28 transmembrane polypeptide, and at least one costimulatory domain comprising at least one CD28 costimulatory polypeptide. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide. [0046] The present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, wherein the anti- CD276 scFv comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 12, a hinge domain comprising a CD28 hinge polypeptide, wherein the CD28 hinge polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 40, a transmembrane domain comprising a CD28 transmembrane polypeptide, wherein the CD28 transmembrane polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 44, and at least one costimulatory domain comprising at least one CD28 costimulatory polypeptide, wherein the at least one CD28 costimulatory polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 48. In some aspects of the preceding anti- CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide, wherein the GMCSF signal peptide comprises an amino acid sequence that is 97%, 98%, or 99% identical to SEQ ID NO: 58. [0047] The present disclosure provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, wherein the anti- CD276 scFv comprises the amino acid sequence of SEQ ID NO: 12, a hinge domain comprising a CD28 hinge polypeptide, wherein the CD28 hinge polypeptide comprises the amino acid sequence of SEQ ID NO: 40, a transmembrane domain comprising a CD28 transmembrane polypeptide, wherein the CD28 transmembrane polypeptide comprises the amino acid sequence of SEQ ID NO: 44, and at least one costimulatory domain comprising at Attorney Docket No.: UNCO-064/001WO 300978-2237 least one CD28 costimulatory polypeptide, wherein the at least one CD28 costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 48. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide, wherein the GMCSF signal peptide comprises the amino acid sequence of SEQ ID NO: 58. [0048] In some aspects, a an anti-CD276 CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 63. [0049] The present disclosure also provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and at least one costimulatory domain comprising at least one 4- 1BB costimulatory polypeptide. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide. [0050] The present disclosure also provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, wherein the anti- CD276 scFv comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 12, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 46, and at least one costimulatory domain comprising at least one 4-1BB costimulatory polypeptide, wherein the at least one 4- 1BB costimulatory polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 50. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide, wherein the GMCSF signal peptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 58. [0051] The present disclosure also provides anti-CD276 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, wherein the anti- Attorney Docket No.: UNCO-064/001WO 300978-2237 CD276 scFv comprises the amino acid sequence of SEQ ID NO: 12, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises the amino acid sequence of SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises the amino acid sequence of SEQ ID NO: 46, and at least one costimulatory domain comprising at least one 4-1BB costimulatory polypeptide, wherein the at least one 4-1BB costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 50. In some aspects of the preceding anti-CD276 CAR polypeptides, the signal peptide can comprise a GMCSF signal peptide, wherein the GMCSF signal peptide comprises the amino acid sequence of SEQ ID NO: 58. [0052] In some aspects, a an anti-CD276 CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 64. [0053] Anti-CD99 CAR polypeptides [0054] The present disclosure also provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, an anti-CD99 antigen binding domain, a transmembrane domain and an activation domain. [0055] The present disclosure also provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, an anti-CD99 antigen binding domain, a transmembrane domain and at least one costimulatory domain. [0056] In some aspects, the anti-CD99 CAR polypeptides of the present disclosure can further comprise a hinge domain located between the anti-CD99 antigen binding domain and the transmembrane domain. Accordingly, present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C- terminus, an anti-CD99 antigen binding domain, a hinge domain, a transmembrane domain and an activation domain. The present disclosure also provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, an anti-CD99 antigen binding domain, a hinge domain, a transmembrane domain and at least one costimulatory domain. [0057] In some aspects, the anti-CD99 CAR polypeptides of the present disclosure can further comprise a signal peptide at the N-terminus of the anti-CD99 CAR polypeptide. Accordingly, the present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an Attorney Docket No.: UNCO-064/001WO 300978-2237 anti-CD99 antigen binding domain, a transmembrane domain and an activation domain. The present disclosure also provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti- CD99 antigen binding domain, a transmembrane domain and at least one costimulatory domain. As described supra, the anti-CD99 CAR polypeptides of the present disclosure can also comprise a hinge domain. Accordingly, the present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C- terminus, a signal peptide, an anti-CD99 antigen binding domain, a hinge domain, a transmembrane domain, and an activation domain. The present disclosure also provides anti- CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N- terminus to C-terminus, a signal peptide, an anti-CD99 antigen binding domain, a hinge domain, a transmembrane domain and at least one costimulatory domain. [0058] The anti-CD99 antigen binding domains, the transmembrane domains, the costimulatory domains, the signal peptides, the hinge domains, and the activation domains of the anti-CD99 CAR polypeptides of the present disclosure can be selected from any of the anti-CD99 antigen binding domains, the transmembrane domains, the costimulatory domains, the signal peptides, the hinge domains, and the activation domains of the anti-CD99 CAR polypeptides described in further detail herein. [0059] The following are exemplary anti-CD99 CAR polypeptides of the present disclosure. [0060] The present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti- CD99 antigen binding domain comprising an anti-CD99 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and an activation domain comprising a CD3ȗ activation polypeptide. In some aspects of the preceding anti-CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide. [0061] The present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti- CD99 antigen binding domain comprising an anti-CD99 scFv, wherein the anti-CD99 scFv comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 38, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises an amino acid sequence that is at least 97%, Attorney Docket No.: UNCO-064/001WO 300978-2237 98%, 99% identical to SEQ ID NO: 46, and an activation domain comprising a CD3ȗ activation polypeptide, wherein the CD3ȗ activation polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 52. In some aspects of the preceding anti-CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide, wherein the CD8 signal peptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 56. [0062] The present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti- CD99 antigen binding domain comprising an anti-CD99 scFv, wherein the anti-CD99 scFv comprises the amino acid sequence of SEQ ID NO: 38, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises the amino acid sequence of SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises the amino acid sequence of SEQ ID NO: 46, and an activation domain comprising a CD3ȗ activation polypeptide, wherein the CD3ȗ activation polypeptide comprises the amino acid sequence of SEQ ID NO: 52. In some aspects of the preceding anti-CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide, wherein the CD8 signal peptide comprises the amino acid sequence of SEQ ID NO: 56. [0063] In some aspects, a an anti-CD99 CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 65. [0064] The present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti- CD99 antigen binding domain comprising an anti-CD99 scFv, a hinge domain comprising a CD28 hinge polypeptide, a transmembrane domain comprising a CD28 transmembrane polypeptide, and at least one costimulatory domain comprising at least one CD28 costimulatory polypeptide. In some aspects of the preceding anti-CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide. [0065] The present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti- CD99 antigen binding domain comprising an anti-CD99 scFv, wherein the anti-CD99 scFv comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 38, a hinge domain comprising a CD28 hinge polypeptide, wherein the CD28 hinge Attorney Docket No.: UNCO-064/001WO 300978-2237 polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 40, a transmembrane domain comprising a CD28 transmembrane polypeptide, wherein the CD28 transmembrane polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 44, and at least one costimulatory domain comprising at least one CD28 costimulatory polypeptide, wherein the at least one CD28 costimulatory polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 48. In some aspects of the preceding anti-CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide, wherein the CD8 signal peptide comprises an amino acid sequence that is 97%, 98%, or 99% identical to SEQ ID NO: 56. [0066] The present disclosure provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti- CD99 antigen binding domain comprising an anti-CD99 scFv, wherein the anti-CD99 scFv comprises the amino acid sequence of SEQ ID NO: 38, a hinge domain comprising a CD28 hinge polypeptide, wherein the CD28 hinge polypeptide comprises the amino acid sequence of SEQ ID NO: 40, a transmembrane domain comprising a CD28 transmembrane polypeptide, wherein the CD28 transmembrane polypeptide comprises the amino acid sequence of SEQ ID NO: 44, and at least one costimulatory domain comprising at least one CD28 costimulatory polypeptide, wherein the at least one CD28 costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 48. In some aspects of the preceding anti- CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide, wherein the CD8 signal peptide comprises the amino acid sequence of SEQ ID NO: 56. [0067] In some aspects, a an anti-CD99 CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 61. [0068] The present disclosure also provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD99 antigen binding domain comprising an anti-CD99 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and at least one costimulatory domain comprising at least one 4- 1BB costimulatory polypeptide. In some aspects of the preceding anti-CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0069] The present disclosure also provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD99 antigen binding domain comprising an anti-CD99 scFv, wherein the anti-CD99 scFv comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 38, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 46 and at least one costimulatory domain comprising at least one 4-1BB costimulatory polypeptide, wherein the at least one 4-1BB costimulatory polypeptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 50. In some aspects of the preceding anti-CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide, wherein the CD8 signal peptide comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 56. [0070] The present disclosure also provides anti-CD99 CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-terminus, a signal peptide, an anti-CD99 antigen binding domain comprising an anti-CD99 scFv, wherein the anti-CD99 scFv comprises the amino acid sequence of SEQ ID NO: 38, a hinge domain comprising a CD8 hinge polypeptide, wherein the CD8 hinge polypeptide comprises the amino acid sequence of SEQ ID NO: 42, a transmembrane domain comprising a CD8 transmembrane polypeptide, wherein the CD8 transmembrane polypeptide comprises the amino acid sequence of SEQ ID NO: 46, and at least one costimulatory domain comprising at least one 4-1BB costimulatory polypeptide, wherein the at least one 4-1BB costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 50. In some aspects of the preceding anti- CD99 CAR polypeptides, the signal peptide can comprise a CD8 signal peptide, wherein the CD8 signal peptide comprises the amino acid sequence of SEQ ID NO: 56. [0071] In some aspects, a an anti-CD99 CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 60. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0072] Antigen Binding Domains [0073] In some aspects, the antigen binding domains of the CAR polypeptides of the present disclosure can comprise an antibody specific for the cognate antigen for that CAR polypeptide (i.e. either CD99 or CD276), or an antigen binding fragment thereof. [0074] Accordingly, in some aspects, an anti-CD276 antigen binding domain can comprise, consist essentially of, or consist of an anti-CD276 antibody, or an antigen binding fragment thereof. Any suitable anti-CD276 antibody can be used, including those known in the art, such as those put forth in US Patent No.10730941. [0075] In some aspects, an anti-CD276 antigen binding domain can comprise, consist essentially of, or consist of an anti-CD276 scFv. Any suitable anti-CD276 scFvs can be used, including those known in the art, such as those put forth or derived from US Patent No. 10562952. [0076] In some aspects, an anti-CD276 scFv can comprise a CDHR1 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 1, a CDRH2 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 2, a CDRH3 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 3, a CDRL1 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 4, a CDRL2 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 5, and a CDHL3 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 6. [0077] In some aspects, an anti-CD276 scFv can comprise a CDHR1 having an amino acid sequence of SEQ ID NO: 1, a CDRH2 having an amino acid sequence of SEQ ID NO: 2, a CDRH3 having an amino acid sequence of SEQ ID NO: 3, a CDRL1 having an amino acid sequence of SEQ ID NO: 4, a CDRL2 having an amino acid sequence of SEQ ID NO: 5, and a CDHL3 having an amino acid sequence of SEQ ID NO: 6. [0078] In some aspects, an anti-CD276 scFv can comprise a VH domain comprising an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 7. Accordingly, a nucleic acid sequence encoding for the VH domain can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 8. [0079] In some aspects, an anti-CD276 scFV can comprise a VL domain comprising an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 9. Accordingly, a nucleic acid sequence encoding for the VL domain can comprise, consist Attorney Docket No.: UNCO-064/001WO 300978-2237 essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 10. [0080] In some aspects, an anti-CD276 scFv can comprise a linker domain that connects the VL domain and the VH domain, wherein the linker domain comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 11. [0081] In some aspects, an anti-CD276 scFv can comprise a VH domain comprising the amino acid sequence of SEQ ID NO: 7. In some aspects, an anti-CD276 scFV can comprise a VL domain comprising the amino acid sequence of SEQ ID NO: 9. In some aspects, an anti- CD276 scFv can comprise a linker domain that connects the VL domain and the VH domain, wherein the linker domain comprises the amino acid sequence of SEQ ID NO: 11. [0082] In some aspects, an anti-CD276 scFv can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 12. Accordingly, a nucleic acid sequence encoding for an anti-CD276 scFv can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 13. [0083] In some aspects, an anti-CD99 antigen binding domain can comprise, consist essentially of, or consist of an anti-CD99 antibody, or an antigen binding fragment thereof. Any suitable anti-CD99 antibody can be used, including those known in the art, such as those put forth in PCT International Application No. PCT/US2023/067715 (published as WO/2023/235767) and US Patent No.8710194. [0084] In some aspects, an anti-CD99 antigen binding domain can comprise, consist essentially of, or consist of an anti-CD99 scFv. Any suitable anti-CD99 scFv can be used, including those known in the art, such as those put forth in and derived from PCT International Application No. PCT/US2023/067715, (published as WO/2023/235767) and US Patent No.8710194. [0085] In some aspects, an anti-CD99 scFv can comprise a CDHR1 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 14, a CDRH2 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 15, a CDRH3 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 16, a CDRL1 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 17, a CDRL2 having an amino acid sequence that is at least 97%, Attorney Docket No.: UNCO-064/001WO 300978-2237 98%, or 99% identical to SEQ ID NO: 18, a CDHL3 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 19. [0086] In some aspects, an anti-CD99 scFv can comprise a CDHR1 having an amino acid sequence of SEQ ID NO: 14, a CDRH2 having an amino acid sequence of SEQ ID NO: 15, a CDRH3 having an amino acid sequence of SEQ ID NO: 16, a CDRL1 having an amino acid sequence of SEQ ID NO: 17, a CDRL2 having an amino acid sequence of SEQ ID NO: 18, a CDHL3 having an amino acid sequence of SEQ ID NO: 19. [0087] In some aspects, an anti-CD99 scFv can comprise a VH domain comprising an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 20. Accordingly, a nucleic acid sequence encoding for the VH domain can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 21. [0088] In some aspects, an anti-CD99 scFV can comprise a VL domain comprising an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 22. Accordingly, a nucleic acid sequence encoding for the VL domain can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 23. [0089] In some aspects, an anti-CD99 scFv can comprise a linker domain that connects the VL domain and the VH domain, wherein the linker domain comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 24. [0090] In some aspects, an anti-CD99 scFv can comprise a VH domain comprising the amino acid sequence of SEQ ID NO: 20. In some aspects, an anti-CD99 scFV can comprise a VL domain comprising the amino acid sequence of SEQ ID NO: 22. In some aspects, an anti- CD99 scFv can comprise a linker domain that connects the VL domain and the VH domain, wherein the linker domain comprises the amino acid sequence of SEQ ID NO: 24. [0091] In some aspects, an anti-CD99 scFv can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 25. Accordingly, a nucleic acid sequence encoding for an anti-CD99 scFv can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 26. [0092] In some aspects, an anti-CD99 scFv can comprise a CDHR1 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 27, a CDRH2 having an Attorney Docket No.: UNCO-064/001WO 300978-2237 amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 28, a CDRH3 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 29, a CDRL1 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 30, a CDRL2 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 31, a CDHL3 having an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 32. [0093] In some aspects, an anti-CD99 scFv can comprise a CDHR1 having an amino acid sequence of SEQ ID NO: 27, a CDRH2 having an amino acid sequence of SEQ ID NO: 28, a CDRH3 having an amino acid sequence of SEQ ID NO: 29, a CDRL1 having an amino acid sequence of SEQ ID NO: 30, a CDRL2 having an amino acid sequence of SEQ ID NO: 31, a CDHL3 having an amino acid sequence of SEQ ID NO: 32. [0094] In some aspects, an anti-CD99 scFv can comprise a VH domain comprising an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 33. Accordingly, a nucleic acid sequence encoding for the VH domain can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 34. [0095] In some aspects, an anti-CD99 scFV can comprise a VL domain comprising an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 35. Accordingly, a nucleic acid sequence encoding for the VL domain can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 36. [0096] In some aspects, an anti-CD99 scFv can comprise a linker domain that connects the VL domain and the VH domain, wherein the linker domain comprises an amino acid sequence that is at least 97%, 98%, or 99% identical to SEQ ID NO: 37. [0097] In some aspects, an anti-CD99 scFv can comprise a VH domain comprising the amino acid sequence of SEQ ID NO: 33. In some aspects, an anti-CD99 scFV can comprise a VL domain comprising the amino acid sequence of SEQ ID NO: 35 In some aspects, an anti- CD99 scFv can comprise a linker domain that connects the VL domain and the VH domain, wherein the linker domain comprises the amino acid sequence of SEQ ID NO: 37. [0098] In some aspects, an anti-CD99 scFv can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 38. Accordingly, a nucleic acid sequence encoding for an anti-CD99 scFv can comprise, consist essentially of, Attorney Docket No.: UNCO-064/001WO 300978-2237 or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 39. [0099] "Antibody" as used herein refers to monoclonal or polyclonal antibodies. The term "monoclonal antibodies," as used herein, refers to antibodies that are produced by a single clone of B-cells and bind to the same epitope. In contrast, "polyclonal antibodies" refer to a population of antibodies that are produced by different B-cells and bind to different epitopes of the same antigen. A whole antibody typically consists of four polypeptides: two identical copies of a heavy (H) chain polypeptide and two identical copies of a light (L) chain polypeptide. Each of the heavy chains contains one N-terminal variable (VH) region and three C-terminal constant (CHL CH2 and CH3) regions, and each light chain contains one N- terminal variable (VL) region and one C-terminal constant (CL) region. The variable regions of each pair of light and heavy chains form the antigen binding site of an antibody. The VH and VL regions have a similar general structure, with each region comprising four framework regions, whose sequences are relatively conserved. The framework regions are connected by three complementarity determining regions (CDRs). The three CDRs, known as CDR1, CDR2, and CDR3, form the "hypervariable region" of an antibody, which is responsible for antigen binding. [0100] The terms "fragment of an antibody," "antibody fragment,", "functional fragment of an antibody," "antigen-binding portion," and “antigen-binding fragment” are used interchangeably herein to mean one or more fragments or portions of an antibody that retain the ability to specifically bind to an antigen (see, generally, Holliger et al. (2005) Nat. Biotech.23(9):1126-29). The antibody fragment desirably comprises, for example, one or more CDRs, the variable region (or portions thereof), the constant region (or portions thereof), or combinations thereof. [0101] Examples of antibody fragments include, but are not limited to, (i) a Fab fragment, which is a monovalent fragment comprising the VL, VH, CL, and CH1 domains; (ii) a F(ab')2 fragment, which is a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the stalk region; (iii) a Fv fragment comprising the VL and VH domains of a single arm of an antibody; (iv) a single chain Fv (scFv), which is a monovalent molecule comprising the two domains of the Fv fragment (i.e., VL and VH) joined by a synthetic linker, which enables the two domains to be synthesized as a single polypeptide chain (see, e.g., Bird et al. (1988), Science 242: 423-6; Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85: 5879-83; and Osbourn et al. (1998) Nat. Biotechnol.16: 778-81) and (v) a diabody, which is a dimer of polypeptide chains, wherein each polypeptide chain comprises a VH connected Attorney Docket No.: UNCO-064/001WO 300978-2237 to a VL by a peptide linker that is too short to allow pairing between the VH and VL on the same polypeptide chain, thereby driving the pairing between the complementary domains on different VH-VL polypeptide chains to generate a dimeric molecule having two functional antigen binding sites. Antibody fragments are known in the art and are described in more detail in, e.g., U.S. Patent Application Publication 2009/0093024 Al. [0102] Accordingly, in some aspects, the antigen binding domain of a CAR polypeptide described herein comprises an scFv comprising a VH domain and a VL domain, wherein the VH comprises a CDRH1, a CDRH2, and a CDRH3 each comprising the amino acid sequence of a CDRH1, a CDRH2, and a CDRH3 of an anti-CD276 or anti-CD99 antibody known in the art, and wherein and the VL comprises a CDRL1, a CDRL2, and a CDRL3 each comprising the amino acid sequence of a CDRL1, a CDRL2, and a CDRL3 of the same anti- CD276 or anti-CD99 antibody known in the art. Determination of CDR regions is well within the skill of the art. It is understood that in some aspects, CDRs can be a combination of the Kabat and Chothia CDR (also termed “combined CRs” or “extended CDRs”). [0103] In some aspects, the CDRs are the Kabat CDRs. In other aspects, the CDRs are the Chothia CDRs. In other aspects, the CDRs are IMGT CDRs. In other words, in aspects with more than one CDR, the CDRs may be any of Kabat, Chothia, IMGT combination CDRs, or combinations thereof. [0104] Transmembrane Domains [0105] The anti-CD99 CAR polypeptides of the present disclosure and the anti-CD276 CAR polypeptides of the present disclosure are intended to be expressed on the surface membrane of the cell. Accordingly, the anti-CD99 CAR polypeptides of the present disclosure and the anti-CD276 CAR polypeptides of the present disclosure can comprise a transmembrane domain. [0106] As would be appreciated by the skilled artisan, a transmembrane domain may be any protein structure which is thermodynamically stable in a membrane. This is typically an alpha helix comprising of several hydrophobic residues. The transmembrane domain of any transmembrane protein can be used to supply the transmembrane portion of the anti-CD99 CAR polypeptides and the anti-CD276 CAR polypeptides of the present disclosure. The presence and span of a transmembrane domain of a protein can be determined by those skilled in the art using the DeepTMHMM algorithm (see Hallgren et al. bioRxiv (2022). DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks. https://doi.org/10.1101/2022.04.08.487609), or any equivalent algorithm known in the art. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0107] Transmembrane domains can be derived either from a natural or from a synthetic source. Transmembrane domains can be derived from any membrane-bound or transmembrane protein. As non-limiting examples, the transmembrane polypeptide can be a subsequence or subunit of the T cell receptor such as Į, ȕ, Ȗ or į, polypeptide constituting CD3 complex, IL-2 receptor p55 (a chain), p75 (ȕ chain) or Ȗ chain, subunit chain of Fc receptors, in particular FcȖ receptor III or CD proteins. Alternatively, transmembrane domains can be synthetic and can comprise, consist essentially of, or consist of hydrophobic residues such as leucine and valine. [0108] In some aspects, a transmembrane domain can comprise, consist essentially of, or consist of a CD8 transmembrane domain. [0109] In some aspects, a CD8 transmembrane domain can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 46. Accordingly, a nucleic acid sequence encoding for a CD8 transmembrane domain can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 47. [0110] In some aspects, a transmembrane domain can comprise, consist essentially of, or consist of a CD28 transmembrane domain. [0111] In some aspects, a CD28 transmembrane domain can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 44. Accordingly, a nucleic acid sequence encoding for CD28 transmembrane domain can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 45. [0112] Costimulatory Domains [0113] In some aspects, the costimulatory domains of the CAR polypeptides of the present disclosure can comprise the intracellular domain, or a fragment thereof, of a costimulatory molecule. [0114] A “costimulatory molecule” as used herein refers to the cognate binding partner on an immune cell, e.g., a T cell, that specifically binds with a co-stimulatory ligand, thereby mediating a costimulatory response by the cell, such as, but not limited to proliferation. Costimulatory molecules include, but are not limited to an MHC class I molecule, BTLA and Attorney Docket No.: UNCO-064/001WO 300978-2237 Toll ligand receptor. Examples of costimulatory molecules include CD27, CD28, CD8, 4- 1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, CD276 and a ligand that specifically binds with CD83 and the like. [0115] A “costimulatory ligand” refers to a molecule on an antigen presenting cell that specifically binds a cognate costimulatory signal molecule on an immune cell, e.g., a T cell, thereby providing a signal which, in addition to the primary signal provided by, for instance, binding of a TCR/CD3 complex with an MHC molecule loaded with peptide, mediates a T cell response, including, but not limited to, proliferation activation, differentiation and the like. A co-stimulatory ligand can include but is not limited to CD7, B7-1 (CD80), B7-2 (CD86), PD-L1, PD-L2, 4-1BBL, OX40L, inducible costimulatory igand (ICOS-L), intercellular adhesion molecule (ICAM, CD30L, CD40, CD70, CD83, HLA-G, MICA, M1CB, HVEM, lymphotoxin ȕ receptor, 3/TR6, ILT3, ILT4, an agonist or antibody that binds Toll ligand receptor and a ligand that specifically binds with CD276. A costimulatory ligand also encompasses, inter alia, an antibody that specifically binds with a co-stimulatory molecule present on a T cell, such as but not limited to, CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LTGHT, NKG2C, CD276, a ligand that specifically binds with CD83. [0116] In some aspects, a costimulatory domain can comprise, consist essentially of, or consist of the intracellular domain, or a fragment thereof, of 4-1BB (CD137). Such costimulatory domains are referred to herein as 4-1BB costimulatory polypeptides. Accordingly, a costimulatory domain of a CAR polypeptide of the present disclosure can comprise, consist essentially of, or consist of at least one 4-1BB costimulatory polypeptide. [0117] In some aspects, a 4-1BB costimulatory polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 50. Accordingly, a nucleic acid sequence encoding for a 4-1BB costimulatory polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 51. [0118] In some aspects, a costimulatory domain can comprise, consist essentially of, or consist of the intracellular domain, or a fragment thereof of, CD28. Such costimulatory domains are referred to herein as CD28 costimulatory polypeptides. Accordingly, a Attorney Docket No.: UNCO-064/001WO 300978-2237 costimulatory domain of a CAR polypeptide of the present disclosure can comprise, consist essentially of, or consist of at least one CD28 costimulatory polypeptide. [0119] In some aspects, a CD28 costimulatory polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 48. Accordingly, a nucleic acid sequence encoding for a CD28 costimulatory polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 49. [0120] Activation Domain [0121] In some aspects, the activation domains of the CAR polypeptides of the present disclosure can comprise, consist essentially of, or consist of cytoplasmic signaling sequences that initiate antigen-dependent primary activation. As would be apricated by the skilled artisan, primary cytoplasmic signaling sequences can comprise, consist essentially of, or consist of signaling motifs which are known as immunoreceptor tyrosine-based activation motifs (ITAMs). ITAMs are well defined signaling motifs found in the intracytoplasmic tail of a variety of receptors that serve as binding sites for syk/zap70 class tyrosine kinases. Examples of ITAMs, including, but are not limited to, those derived from TCRȗ, FcRȖ, FcRȕ, FcRİ, CD3Ȗ, CD3į, CD3İ, CD3ȗ, CD5, CD22, CD79a, CD79b and CD66d. [0122] In some aspects, an activation domain can comprise, consist essentially of, or consist of a CD3ȗ activation polypeptide. [0123] In some aspects, a CD3ȗ activation polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 52. Accordingly, a nucleic acid sequence encoding for a CD3ȗ activation polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 53. [0124] Hinge Domains [0125] In some aspects, a hinge domain of a CAR polypeptide of the present disclosure refers to a polypeptide that is located between the antigen binding domain and the transmembrane domain. Without wishing to be bound by theory, a hinge domain can provide more flexibility and accessibility for the antigen binding domain. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0126] In some aspects, a hinge domain may comprise, consist essentially or, or consist of up to 300 amino acids. [0127] In some aspects, a hinge domain can comprise, consist essentially or, or consist of 10 to 100 amino acids or 25 to 50 amino acids. [0128] In some aspects, a hinge domain can be derived from all or part of naturally occurring molecules, such as from all or part of the extracellular region of CD8, CD4, CD28, 4-1BB, or IgG (in particular, the hinge region of an IgG), or from all or part of an antibody heavy-chain constant region. [0129] In some aspects, a hinge domain can be a synthetic sequence that corresponds to a naturally occurring hinge sequence, or may be an entirely synthetic hinge sequence. In some aspects, a hinge domain can comprise, consist essentially or, or consist of a subsequence of CD8Į, an IgG1, or an FcȖRIIIĮ. [0130] In some aspects, a hinge domain can comprise, consist essentially of, or consist of a CD28 hinge polypeptide. [0131] In some aspects, a CD28 hinge polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 40. Accordingly, a nucleic acid sequence encoding for a CD28 hinge polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 41. [0132] In some aspect, a hinge domain can comprise, consist essentially of, or consist of a CD8 hinge polypeptide. [0133] In some aspects, a CD8 hinge polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 42. Accordingly, a nucleic acid sequence encoding for a CD8 hinge polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 43. [0134] Signal peptides [0135] As used herein, the term “signal peptide” refers to a peptide which functions to direct the polypeptide to which its attached to the secretory pathway. As would be appreciated by the skilled artisan, in contexts wherein a polypeptide of the present disclosure comprises both Attorney Docket No.: UNCO-064/001WO 300978-2237 a signal peptide and a transmembrane domain, the signal peptide functions to direct that polypeptide to the secretory pathway such that the polypeptide eventually embedded within a membrane, preferably the cellular membrane. Signal peptides are well known in the art. Accordingly, a signal peptide within the polypeptides of the present disclosure can be any signal peptide known in the art that is sufficient to direct the polypeptide to which its attached to the secretory pathway. [0136] In some aspects, a signal peptide can comprise, consist essentially of, or consist of a CD8 signal peptide. [0137] In some aspects, a CD8 signal peptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 56. Accordingly, a nucleic acid sequence encoding for a CD8 signal peptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: [0138] In some aspects, a signal peptide can comprise, consist essentially of, or consist of a GMCSF signal peptide. [0139] In some aspects, a GMCSF signal peptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 58. Accordingly, a nucleic acid sequence encoding for a GMCSF signal peptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 59. [0140] Logic Pairs of CAR polypeptides [0141] The present disclosure provides logic pairs of CAR polypeptides, wherein a logic pair of CAR polypeptides comprises, consists essentially of, or consists of, an anti-CD276 CAR polypeptide of the present disclosure and an anti-CD99 CAR of the present disclosure. [0142] Without wishing to be bound by theory, the pairings of an anti-CD276 CAR polypeptide and an anti-CD99 CAR polypeptide allows for the manufacture of “logic gated” CAR T cells. These logic gated CAR T cells express a logic pair of CAR polypeptides and achieve full activation only when they encounter a cell that expresses both CD99 and CD276. Such T cells are also referred to herein as CD99/CD276 logic gated CAR-T cells. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0143] Without wishing to be bound by theory, such logic gated CAR T cells exhibit less off- target toxicity because the co-expression of CD99 and CD276 is a more specific marker for certain types of cancer cells (e.g. DIPG cells), as compared to either CD99 and CD276 alone. That is, if the logic gated CAR T cells encounter a non-cancerous cell that expresses only CD99 and not CD276 or a non-cancerous cell that expresses only CD276 and not CD99, the logic gated CAR T cells will not be activated by these non-cancerous cells, thereby sparing the non-cancerous cells. [0144] In some aspects of the logic pairs of CAR polypeptides, one of the CAR polypeptides of the pair has an intracellular domain that comprises one or more costimulatory domains and does not comprise an activation domain, and the other CAR polypeptide of the pair has an intracellular domain that comprises an intracellular domain and does not comprise any costimulatory domains. That is, as compared to “traditional CAR formats”, the logic pairs of CAR polypeptides of the present disclosure separates the costimulatory domains and the activation domains onto separate molecules. Without wishing to be bound by theory, by separating the costimulatory domains and intracellular domains onto separate CAR molecules that are specific to different antigens (e.g. CD99 and CD276), both CAR molecules must engage both antigens on the target cell in order to achieve full activation of the CAR T cell. [0145] In some aspects of the logic pairs of CAR polypeptides, the anti-CD276 CAR polypeptide of the logic pair comprises one or more costimulatory domains and the anti- CD99 CAR polypeptide of the logic pair comprises an activation domain. In some aspects, the one or more costimulatory domains comprise CD28 costimulatory polypeptides and/or 4- 1BB costimulatory polypeptides. In some aspects, the activation domain comprises one or more CD3ȗ activation polypeptides. [0146] In some aspects of the logic pairs of CAR polypeptides, the anti-CD99 CAR polypeptide of the logic pair comprises one or more costimulatory domains and the anti- CD276 CAR polypeptide of the logic pair comprises an activation domain. In some aspects, the one or more costimulatory domains comprise CD28 costimulatory polypeptides and/or 4- 1BB costimulatory polypeptides. In some aspects, the activation domain comprises one or more CD3ȗ activation polypeptides. [0147] Accordingly, the present disclosure provides compositions comprising a logic pair of CAR polypeptides of the present disclosure. In some aspects, this compositions takes the form or a cell or populations of cells that express the logic pair of CAR polypeptides. In some aspects, the compositions takes the form of nucleic acid molecules (e.g. vectors) comprising Attorney Docket No.: UNCO-064/001WO 300978-2237 sequences that encode for the logic pair of CAR polypeptides. These compositions are described in further detail herein. [0148] In some aspects the logic pair of CARs can be expressed as a bicistronic CAR polypeptide that comprises, consists essentially of, or consists of, from N-terminus to C- Terminus, a first CAR polypeptide, a self-cleaving peptide, and a second CAR polypeptide. Accordingly, the present disclosure provides bicistronic CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-Terminus, an anti-CD276 CAR polypeptide, a self-cleaving peptide, and an anti-CD99 CAR polypeptide of the present disclosure. The present disclosure also provides bicistronic CAR polypeptides comprising, consisting essentially of, or consisting of, from N-terminus to C-Terminus, an anti-CD99 CAR polypeptide, a self-cleaving peptide, and an anti-CD276 CAR polypeptide of the present disclosure. [0149] In some aspects, a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 66. Accordingly, a nucleic acid sequence encoding for a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 67. [0150] In some aspects, a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 68. Accordingly, a nucleic acid sequence encoding for a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 69. [0151] In some aspects, a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 70. Accordingly, a nucleic acid sequence encoding for a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 71. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0152] In some aspects, a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 72. Accordingly, a nucleic acid sequence encoding for a bicistronic CAR polypeptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 73. [0153] Functional Variants of the Polypeptides of the Present Disclosure [0154] The present disclosure also contemplates functional variants of the CAR polypeptides disclosed and described herein. The term "functional variant" as used herein refers to a CAR polypeptide having substantial or significant sequence identity or similarity to a parent CAR where the functional variant retains the biological activity of the parent CAR polypeptide of which it is a variant. Functional variants encompass, for example, those variants of the CAR polypeptide described herein (the parent CAR polypeptide) that retain the ability to recognize target cells to a similar extent, the same extent, or to a higher extent, as the parent CAR polypeptide. In reference to the parent CAR the functional variant can, for instance, be at least about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more identical in amino acid sequence to the parent CAR. [0155] A functional variant can, for example, comprise the amino acid sequence of the parent CAR with at least one conservative amino acid substitution. Alternatively, or additionally, the functional variants can comprise the amino acid sequence of the parent CAR with at least one non-conservative amino acid substitution. In this case, it is preferable for the non- conservative amino acid substitution to not interfere with or inhibit the biological activity of the functional variant. The non-conservative amino acid substitution may enhance the biological activity of the functional variant, such that the biological activity of the functional variant is increased as compared to the parent CAR. [0156] A conservative substitution of an amino acid, i.e., replacing an amino acid with a different amino acid of similar properties (e.g., hydrophilicity, degree and distribution of charged regions) is recognized in the art as typically involving a minor change. These minor changes can be identified, in part, by considering the hydropathic index of amino acids, as understood in the art. Kyte et al., J. Mol. Biol.157: 105-132 (1982). The hydropathic index of an amino acid is based on a consideration of its hydrophobicity and charge. Amino acids of similar hydropathic indexes can be substituted and still retain protein function. In an aspect, Attorney Docket No.: UNCO-064/001WO 300978-2237 amino acids having hydropathic indexes of ±2 are substituted. The hydrophilicity of amino acids can also be used to reveal substitutions that would result in proteins retaining biological function. A consideration of the hydrophilicity of amino acids in the context of a polypeptide permits calculation of the greatest local average hydrophilicity of that polypeptide, a useful measure that has been reported to correlate well with antigenicity and immunogenicity. U.S. Patent No.4,554,101, incorporated fully herein by reference. [0157] Substitution of amino acids having similar hydrophilicity values can result in polypeptides retaining biological activity, for example immunogenicity. Substitutions can be performed with amino acids having hydrophilicity values within ±2 of each other. Both the hydrophobicity index and the hydrophilicity value of amino acids are influenced by the particular side chain of that amino acid. Consistent with that observation, amino acid substitutions that are compatible with biological function are understood to depend on the relative similarity of the amino acids, and particularly the side chains of those amino acids, as revealed by the hydrophobicity, hydrophilicity, charge, size, and other properties. [0158] As used herein, “conservative” amino acid substitutions may be defined as set out in Tables A, B, or C below. In some aspects, fusion polypeptides and/or nucleic acids encoding such fusion polypeptides include conservative substitutions have been introduced by modification of polynucleotides encoding polypeptides of the disclosure. Amino acids can be classified according to physical properties and contribution to secondary and tertiary protein structure. A conservative substitution is a substitution of one amino acid for another amino acid that has similar properties. Exemplary conservative substitutions are set out in Table A. [0159] Table A -- Conservative Substitutions I [0160] Alternately, conservative amino acids can be grouped as described in Lehninger, (Biochemistry, Second Edition; Worth Publishers, Inc. NY, N.Y. (1975), pp.71-77) as set forth in Table B. [0161] Table B -- Conservative Substitutions II Attorney Docket No.: UNCO-064/001WO 300978-2237 [0162] Alternately, exemplary conservative substitutions are set out in Table C. [0163] Table C -- Conservative Substitutions III [0164] It should be understood that the polypeptides of the disclosure are intended to include polypeptides bearing one or more insertions, deletions, or substitutions, or any combination thereof, of amino acid residues as well as modifications other than insertions, deletions, or substitutions of amino acid residues. Polypeptides or nucleic acids of the disclosure may contain one or more conservative substitution. [0165] As used throughout the disclosure, the term “more than one” of the aforementioned amino acid substitutions refers to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more of the recited amino acid substitutions. The term “more than one” may refer to 2, 3, 4, or 5 of the recited amino acid substitutions. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0166] Nucleic Acid Molecules of the Present Disclosure [0167] The present disclosure provides nucleic acid molecules comprising, consisting essentially of, or consisting of one or more nucleic acid sequences encoding for an anti-CD99 CAR polypeptide of the present disclosure. [0168] The present disclosure provides nucleic acid molecules comprising, consisting essentially of, or consisting of one or more nucleic acid sequences encoding for an anti- CD276 CAR polypeptide of the present disclosure. [0169] The present disclosure provides nucleic acid molecules comprising, consisting essentially of, or consisting of one or more nucleic acid sequences encoding for an anti- CD276 CAR polypeptide of the present disclosure and one or more nucleic acid sequences encoding for an anti-CD99 CAR polypeptide of the present disclosure. That is, the present disclosure provides nucleic acid molecules comprising, consisting essentially of, or consisting of one or more nucleic acid sequence encoding for a logic pair of CAR polypeptides. Accordingly, the present disclosure provides nucleic acid molecules comprising, consisting essentially of, or consisting of one or more nucleic acid sequences encoding for bicistronic CAR polypeptide of the present disclosure. [0170] In aspects wherein the nucleic acid molecules of the present disclosure comprise a nucleic acid sequence encoding an anti-CD276 CAR polypeptide and a nucleic acid sequence encoding an anti-CD99 CAR polypeptide, these nucleic acid sequences can be in any order, i.e. the nucleic acids molecules can comprise, from 5’ to 3’, a nucleic acid sequence encoding an anti-CD276 CAR polypeptide of the present disclosure and a nucleic acid sequence encoding an anti-CD99 CAR polypeptide, or the nucleic acid molecules can comprise, from 5’ to 3’, a nucleic acid sequence encoding an anti-CD99 CAR polypeptide and a nucleic acid sequence encoding an anti-CD276 CAR polypeptide of the present disclosure. [0171] In aspects wherein a nucleic acid molecule of the present disclosure comprises two or more nucleic acid sequences encoding for polypeptides (e.g. a nucleic acid sequence encoding for an anti-CD276 CAR polypeptide and a nucleic acid sequence encoding for an anti-CD99 CAR polypeptide of the present disclosure), the nucleic acid sequences encoding the different polypeptides can be separated by one or more nucleic acid sequences that encode a self-cleaving peptide. [0172] As would be appreciated by the skilled artisan, the amino acid sequences of self- cleaving peptides and the nucleic acids sequences encoding said amino acid sequences, are known in the art. Non-limiting examples of self-cleaving peptides include 2A self-cleaving Attorney Docket No.: UNCO-064/001WO 300978-2237 peptide sequences such as the T2A peptide, the E2A peptide, the F2A peptide and the P2A peptide. [0173] In some aspects of the nucleic acid molecules of the present disclosure, the sequence encoding for a self-cleaving peptide is a nucleic acid sequence encoding for a P2A self- cleaving peptide. As would be appreciated by the skilled artisan, a P2A self-cleaving peptide can have an amino acid sequence that comprises, consists essentially of, or consist of an amino acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 54. Accordingly, a nucleic acid sequence encoding for a P2A self-cleaving peptide can comprise, consist essentially of, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 55. [0174] Accordingly, the present disclosure provides nucleic acids comprising, consisting essentially of, or consisting of, from 5’ to 3’, a nucleic acid sequence encoding an anti- CD276 CAR polypeptide of the present disclosure, a nucleic acid sequence encoding a P2A self-cleaving peptide and a nucleic acid sequence encoding an anti-CD99 CAR polypeptide. The present disclosure also provides nucleic acids comprising, consisting essentially of, or consisting of, from 5’ to 3’, a nucleic acid sequence encoding an anti-CD99 CAR polypeptide of the present disclosure, a nucleic acid sequence encoding a P2A self-cleaving peptide and a nucleic acid sequence encoding an anti-CD276 CAR polypeptide. [0175] The present disclosure provides nucleic acid molecules comprising a nucleic acid sequence that comprises, consists essentially or, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 67. [0176] The present disclosure provides nucleic acid molecules comprising a nucleic acid sequence that comprises, consists essentially or, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 69. [0177] The present disclosure provides nucleic acid molecules comprising a nucleic acid sequence that comprises, consists essentially or, or consist of a nucleic acid sequence that is at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 71. [0178] The present disclosure provides nucleic acid molecules comprising a nucleic acid sequence that comprises, consists essentially or, or consist of a nucleic acid sequence that is Attorney Docket No.: UNCO-064/001WO 300978-2237 at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 73. [0179] The present disclosure also provides vectors comprising at least one nucleic acid molecule of the present disclosure. In some aspects, the vector can be a viral vector. In some aspects, the viral vector is an AAV vector or a lentiviral vector. [0180] The present disclosure also encompasses all nucleic acid molecules that are complementary to the nucleic acid molecules described in detail herein. [0181] Cells [0182] The present disclosure provides cells that express at least one anti-CD276 CAR polypeptide of the present disclosure and at least one anti-CD99 CAR polypeptide of the present disclosure. That is, the present disclosure provides cells that express a logic pair of CAR polypeptides of the present disclosure. These cells that express a logic pair of CAR polypeptides of the present disclosure are also referred to herein as “therapeutic cells” as they can be used in methods of treating cancer, as described infra. [0183] Accordingly, the present disclosure provides populations (also referred to herein as pluralities) of cells expressing at least one anti-CD276 CAR polypeptide of the present disclosure and at least one anti-CD99 CAR polypeptide of the present disclosure. That is, the present disclosure populations of cells that express a logic pair of CAR polypeptides of the present disclosure. [0184] In some aspects of the cells of the present disclosure, the expression level of the anti- CD276 CAR polypeptide and the expression level of the anti-CD99 CAR polypeptide can be the same. In some aspects of the cells of the present disclosure, the expression level of the anti-CD276 CAR polypeptide and the expression level of the anti-CD99 CAR polypeptide can be the different. [0185] The present disclosure provides populations of cells, wherein at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%, or at least about 97%, or at least about 99% of the cells in the plurality express both an anti-CD276 CAR polypeptide of the present disclosure and an anti-CD99 CAR polypeptide of the present disclosure. [0186] In some aspects, the cells described above can be immune cells. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0187] As used herein, “immune cell” refers to a cell of hematopoietic origin functionally involved in the initiation and/or execution of innate and/or adaptative immune response. [0188] Examples of immune cells include, but are not limited to, T cells (e.g., regulatory T cells, CAR T cells, CD8+ CAR T cells, CD4+ CAR T cells, CD4+ T cells, CD8+ T cells, peripheral blood (PB) derived T cells, umbilical cord blood (UCB) derived T cells, or gamma-delta T cells), NK cells, NK-like cells, invariant NK cells, NKT cells, cytokine induced killer (CIK) cells, stem cells (e.g., mesenchymal stem cells (MSCs), hematopoietic stem cells, hematopoietic progenitor cells, or induced pluripotent stem (iPSC) cells). In some embodiments, the cells are monocytes or granulocytes, e.g., myeloid cells, macrophages, neutrophils, dendritic cells, mast cells, eosinophils, and/or basophils. [0189] In some aspects, the cells are T cells. [0190] In some aspects, the cells are NK cells. [0191] In some aspects, the cells described above can be tumor infiltrating lymphocytes (“TILs”). As would be appreciated by the skilled artisan, TILs refers to populations of white blood cells that have left the bloodstream of a subject and migrated into a tumor. Populations of TILs can include, but are not limited to, T helper 17 cells (Thl7, CD4+IL17+ T cells), cytotoxic T cells (Tc17, CD8+IL17+ T cells) and regulatory T cells (Treg, CD4+CD25+Foxp3+ T cells), natural killer (NK) cells, dendritic cells and M1 macrophages. As would be appreciated by the skilled artisan, TILs can generally be defined either biochemically, using cell surface markers, or functionally, by their ability to infiltrate tumors and effect treatment. TILs can be generally categorized by expressing one or more of the following biomarkers: CD4, CD8, TCR Įȕ, CD27, CD28, CD56, CCR7, CD45Ra, CD95, PD-1, and CD25. Additionally and alternatively, TILs can be functionally defined by their ability to infiltrate solid tumors upon reintroduction into a subject. [0192] Immune cells may be enriched/purified from any tissue where they reside including, but not limited to, blood (including blood collected by blood banks or cord blood banks), spleen, bone marrow, tissues removed and/or exposed during surgical procedures, and tissues obtained via biopsy procedures. Tissues/organs from which the immune cells are enriched, isolated, and/or purified may be isolated from both living and non-living subjects, wherein the non-living subjects are organ donors. The isolated immune cells may be used directly, or they can be stored for a period of time, such as by freezing. In the case of TILs, the population of TILs can be enriched/purified from a tumor sample obtained from the subject. [0193] The present disclosure also provides pharmaceutical compositions comprising the therapeutic cells or pluralities of therapeutic cells described herein. In some aspects, the Attorney Docket No.: UNCO-064/001WO 300978-2237 pharmaceutical compositions further comprise one or more pharmaceutically acceptable [0194] As used herein, “pharmaceutically acceptable carrier,” “pharmaceutical acceptable excipient,” and “pharmaceutically acceptable diluents” includes any material which, when combined with an active ingredient, allows the ingredient to retain biological activity and is non-reactive with the subject's immune system. Examples include, but are not limited to, any of the standard pharmaceutical carriers such as a phosphate buffered saline solution, water, emulsions such as oil/water emulsion, and various types of wetting agents. Exemplary diluents for aerosol or parenteral administration are phosphate buffered saline (PBS) or normal (0.9%) saline. Compositions comprising such carriers are formulated by well-known conventional methods (see, for example, Remington's Pharmaceutical Sciences, 18th edition, A. Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990; and Remington, The Science and Practice of Pharmacy 21st Ed. Mack Publishing, 2005). [0195] Methods of Use [0196] The present disclosure provides methods of treating cancer in a subject, the method comprising administering to the subject one or more pluralities of therapeutic cells of the present disclosure. [0197] The present disclosure provides one or more pluralities of therapeutic cells of the present disclosure for use in the treatment of cancer in a subject. [0198] The present disclosure provides the use of one or more pluralities of therapeutic cells of the present disclosure for use in the manufacture of a medicament for the treatment of cancer. [0199] The present disclosure provides methods of preventing cancer metastasis in a subject, the method comprising administering to the subject one or more pluralities of therapeutic cells of the present disclosure. [0200] The present disclosure provides one or more pluralities of therapeutic cells of the present disclosure for use in the prevention of cancer metastasis in a subject. [0201] The present disclosure provides the use of one or more pluralities of therapeutic cells of the present disclosure for use in the manufacture of a medicament for the prevention of cancer metastasis. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0202] In some aspects, the plurality or pluralities of therapeutic cells are administered to the subject in a therapeutically effective amount. [0203] In some aspects, the plurality or pluralities of therapeutic cells are administered by intravenous administration. In some aspects, the plurality or pluralities of therapeutic cells are administered by intrathecal administration. In some aspects, the plurality or pluralities of therapeutic cells are administered by intratumoral administration. In some aspects, the plurality or pluralities of therapeutic cells are administered by intrapleural administration, intraperitoneal administration, or intrathoracic administration. [0204] The present disclosure provides methods of treating cancer in the subject, the method comprising administering to the subject one or more pluralities of therapeutic cells of the present disclosure and at least one additional therapy. In some aspects, the at least one additional therapy can be selected from immunotherapy, a stem cell transplant, an anti-cancer therapy, chemotherapy, targeted drug therapy, radiation therapy, or any combination thereof. In some aspects, the at least one additional therapy is radiation therapy. In some aspects, the at least one additional therapy is chemotherapy. In some aspects, the at least one additional therapy comprises the administration of a combination of venetoclax and azacitidine. In some aspects, the subject can be pre-treated with radiation therapy prior to receiving the therapeutic cells of the present disclosure. [0205] In some aspects, the at least one additional therapy and the one or more pluralities of therapeutic cells of the present disclosure can be administered in temporal proximity. [0206] As used herein, the term “temporal proximity” refers to that administration of one therapeutic agent (e.g., one or more pluralities of therapeutic cells of the present disclosure) occurs within a time period before or after the administration of another therapeutic agent (e.g., radiation therapy), such that the therapeutic effect of the one therapeutic agent overlaps with the therapeutic effect of the other therapeutic agent. In some embodiments, the therapeutic effect of the one therapeutic agent completely overlaps with the therapeutic effect of the other therapeutic agent. In some embodiments, “temporal proximity” means that administration of one therapeutic agent occurs within a time period before or after the administration of another therapeutic agent, such that there is a synergistic effect between the one therapeutic agent and the other therapeutic agent. “Temporal proximity” may vary according to various factors, including but not limited to, the age, gender, weight, genetic background, medical condition, disease history, and treatment history of the subject to which the therapeutic agents are to be administered; the disease or condition to be treated or ameliorated; the therapeutic outcome to be achieved; the dosage, dosing frequency, and Attorney Docket No.: UNCO-064/001WO 300978-2237 dosing duration of the therapeutic agents; the pharmacokinetics and pharmacodynamics of the therapeutic agents; and the route(s) through which the therapeutic agents are administered. In some embodiments, “temporal proximity” means within 15 minutes, within 30 minutes, within an hour, within two hours, within four hours, within six hours, within eight hours, within 12 hours, within 18 hours, within 24 hours, within 36 hours, within 2 days, within 3 days, within 4 days, within 5 days, within 6 days, within a week, within 2 weeks, within 3 weeks, within 4 weeks, with 6 weeks, or within 8 weeks. In some embodiments, multiple administration of one therapeutic agent can occur in temporal proximity to a single administration of another therapeutic agent. In some embodiments, temporal proximity may change during a treatment cycle or within a dosing regimen. [0207] The terms "cancer" and "cancerous" refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. [0208] In some aspects, the cancer can be a solid tumor. Exemplary solid tumors can include, but are not limited to, a tumor of an organ selected from the group consisting of pancreas, colon, cecum, stomach, brain, head, neck, ovary, kidney, larynx, sarcoma, lung, bladder, melanoma, prostate, and breast. [0209] In some aspects, the cancer is a hematological cancer. Exemplary hematological tumors include but are not limited to tumors of the bone marrow, T or B cell malignancies, myeloid malignancies, leukemias, lymphomas, blastomas, myelomas. [0210] Further examples of cancers that may be treated using the methods provided herein include, but are not limited to, lung cancer (including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung), cancer of the peritoneum, gastric or stomach cancer (including gastrointestinal cancer and gastrointestinal stromal cancer), pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, prostate cancer, vulval cancer, thyroid cancer, various types of head and neck cancer, and melanoma. [0211] The cancer may specifically be of the following histological type, though it is not limited to these: neoplasm, malignant; carcinoma; carcinoma, undifferentiated; giant and spindle cell carcinoma; small cell carcinoma; papillary carcinoma; squamous cell carcinoma; lymphoepithelial carcinoma; basal cell carcinoma; pilomatrix carcinoma; transitional cell carcinoma; papillary transitional cell carcinoma; adenocarcinoma; gastrinoma, malignant; cholangiocarcinoma; hepatocellular carcinoma; combined hepatocellular carcinoma and cholangiocarcinoma; trabecular adenocarcinoma; adenoid cystic carcinoma; adenocarcinoma Attorney Docket No.: UNCO-064/001WO 300978-2237 in adenomatous polyp; adenocarcinoma, familial polyposis coli; solid carcinoma; carcinoid tumor, malignant; branchiolo-alveolar adenocarcinoma; papillary adenocarcinoma; chromophobe carcinoma; acidophil carcinoma; oxyphilic adenocarcinoma; basophil carcinoma; clear cell adenocarcinoma; granular cell carcinoma; follicular adenocarcinoma; papillary and follicular adenocarcinoma; nonencapsulating sclerosing carcinoma; adrenal cortical carcinoma; endometroid carcinoma; skin appendage carcinoma; apocrine adenocarcinoma; sebaceous adenocarcinoma; ceruminous adenocarcinoma; mucoepidermoid carcinoma; cystadenocarcinoma; papillary cystadenocarcinoma; papillary serous cystadenocarcinoma; mucinous cystadenocarcinoma; mucinous adenocarcinoma; signet ring cell carcinoma; infiltrating duct carcinoma; medullary carcinoma; lobular carcinoma; inflammatory carcinoma; paget's disease, mammary; acinar cell carcinoma; adenosquamous carcinoma; adenocarcinoma w/squamous metaplasia; thymoma, malignant; ovarian stromal tumor, malignant; thecoma, malignant; granulosa cell tumor, malignant; androblastoma, malignant; Sertoli cell carcinoma; leydig cell tumor, malignant; lipid cell tumor, malignant; paraganglioma, malignant; extra-mammary paraganglioma, malignant; pheochromocytoma; glomangiosarcoma; malignant melanoma; amelanotic melanoma; superficial spreading melanoma; lentigo malignant melanoma; acral lentiginous melanomas; nodular melanomas; malignant melanoma in giant pigmented nevus; epithelioid cell melanoma; blue nevus, malignant; sarcoma; fibrosarcoma; fibrous histiocytoma, malignant; myxosarcoma; liposarcoma; leiomyosarcoma; rhabdomyosarcoma; embryonal rhabdomyosarcoma; alveolar rhabdomyosarcoma; stromal sarcoma; mixed tumor, malignant; mullerian mixed tumor; nephroblastoma; hepatoblastoma; carcinosarcoma; mesenchymoma, malignant; brenner tumor, malignant; phyllodes tumor, malignant; synovial sarcoma; mesothelioma, malignant; dysgerminoma; embryonal carcinoma; teratoma, malignant; struma ovarii, malignant; choriocarcinoma; mesonephroma, malignant; hemangiosarcoma; hemangioendothelioma, malignant; kaposi's sarcoma; hemangiopericytoma, malignant; lymphangiosarcoma; osteosarcoma; juxtacortical osteosarcoma; chondrosarcoma; chondroblastoma, malignant; mesenchymal chondrosarcoma; giant cell tumor of bone; ewing's sarcoma; odontogenic tumor, malignant; ameloblastic odontosarcoma; ameloblastoma, malignant; ameloblastic fibrosarcoma; pinealoma, malignant; chordoma; glioma, malignant; ependymoma; astrocytoma; protoplasmic astrocytoma; fibrillary astrocytoma; astroblastoma; glioblastoma; oligodendroglioma; oligodendroblastoma; primitive neuroectodermal; cerebellar sarcoma; ganglioneuroblastoma; neuroblastoma; retinoblastoma; olfactory neurogenic tumor; meningioma, malignant; neurofibrosarcoma; neurilemmoma, malignant; granular cell tumor, Attorney Docket No.: UNCO-064/001WO 300978-2237 malignant; malignant lymphoma; T lymphoblastic leukemia; T lymphoblastic lymphoma; B cell leukaemia; Hodgkin's disease; Hodgkin’s lymphoma; paragranuloma; malignant lymphoma, small lymphocytic; malignant lymphoma, large cell, diffuse; malignant lymphoma, follicular; mycosis fungoides; other specified non-Hodgkin's lymphomas; B cell lymphoma; low grade/follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade/follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; Waldenstrom's macroglobulinemia; malignant histiocytosis; multiple myeloma; mast cell sarcoma; immunoproliferative small intestinal disease; leukemia; lymphoid leukemia; plasma cell leukemia; erythroleukemia; lymphosarcoma cell leukemia; myeloid leukemia; basophilic leukemia; eosinophilic leukemia; monocytic leukemia; mast cell leukemia; megakaryoblastic leukemia; myeloid sarcoma; hairy cell leukemia; chronic lymphocytic leukemia (CLL); chronic myeloid leukemia, acute lymphoblastic leukemia (ALL); acute lymphoblastic lymphoma; acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); myeloproliferative neoplasms; chronic myeloblasts leukemia; diffuse large B cell lymphoma (DLBCL); peripheral T cell lymphoma (PTCL); or anaplastic large cell lymphoma (ALCL). In some embodiments, the cancer comprises a liquid tumor. In some embodiments, the liquid tumor is a leukemia or a lymphoma. In some embodiments, the leukemia or lymphoma is B cell leukemia or B cell lymphoma. [0212] In some aspects, the cancer is a cancer that is characterized by expression of both CD276 and CD99 in the cancerous cells. [0213] In some aspects, the cancer is diffuse intrinsic pontine glioma (DIPG). [0214] In some aspects, the cancer is acute myeloid leukemia (AML). [0215] In some aspects, the cancer is Ewing’s Sarcoma. [0216] In some aspects, the cancer is an ependymoma. In some aspects, the cancer is posterior fossa type A (PFA) ependymoma. [0217] In some aspects, the cancer is an atypical teratoid/rhabdoid tumor (ATRT). [0218] In some aspects, the cancer is an NK/T-cell lymphoma. [0219] In some aspects, the cancer is a large granular lymphocyte leukemia. [0220] In some aspects, the cancer is a chronic myeloid leukemia [0221] In some aspects, the cancer is a glioblastoma. [0222] In some aspects, the cancer is a glioma. [0223] In some aspects, the cancer is an ependymoma. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0224] In some aspects, the cancer is a neuroblastoma. [0225] In some aspects, the cancer is glioblastoma multiforme (GBM). Accordingly, in some aspects, a subject can be an adult having glioblastoma multiforme. [0226] In some aspects, the cancer is recurrent cancer. Accordingly, the cancer can be selected from recurrent DIPG, recurrent AML, and recurrent Ewing’s Sarcoma. [0227] In some aspects, the cancer is refractory to treatment with a treatment that is different from the therapeutic cells of the present disclosure. Accordingly, the cancer can be selected from refractory DIPG, refractory AML, and refractory Ewing’s Sarcoma. [0228] In some aspects, the cancer has metastasized. Accordingly, the cancer can be selected from metastasized DIPG, metastasized AML, and metastasized Ewing’s Sarcoma. [0229] The terms “subject” and “patient” are used interchangeably herein. In some embodiments, the subject treated in accordance with the methods described herein is a human patient. In some aspects, the subject is male. In some aspects, the subject is female. [0230] In some aspects of the methods of the present disclosure, a subject can be at least about 5 years of age, or at least about 10 years of age, or at least about 15 years of age, or at least about 18 years of age, or at least about 20 years of age, or at least about 25 years of age, or at least about 30 years of age, or at least about 35 years of age, or at least about 40 years of age, or at least about 45 years of age, or at least about 50 years of age, or at least about 55 years of age, or at least about 60 years of age, or at least about 65 years of age, or at least about 70 years of age, or at least about 75 years of age, or at least about 80 years of age, or at least about 85 years of age, or at least about 90 years of age, or at least about 95 years of age, or at least about 100 years of age. [0231] In some aspects of the methods of the present disclosure, a subject can be no more than about 5 years of age, or about 10 years of age, or about 15 years of age, or about 18 years of age, or about 20 years of age, or about 25 years of age, or about 30 years of age, or about 35 years of age, or about 40 years of age, or about 45 years of age, or about 50 years of age, or about 55 years of age, or about 60 years of age, or about 65 years of age, or about 70 years of age, or about 75 years of age, or about 80 years of age, or about 85 years of age, or about 90 years of age, or about 95 years of age, or about 100 years of age. [0232] In some aspects of the methods of the present disclosure, a subject can be about 1 year of age to about 20 years of age, or about 2 years of age to about 10 years of age, or about 5 years of age to about 9 years of age, or about 10 years of age to about 15 years of age. [0233] In some aspects, the subject can have received at least one previous therapy. That is, prior to being administered therapeutic cells of the present disclosure, the subject has Attorney Docket No.: UNCO-064/001WO 300978-2237 received at least one previous therapy. In some aspects, the subject can be nonresponsive to the at least one previous therapy. In some aspects, the subject can have been initially responsive to the at least one previous therapy, but then became unresponsive over the course of treatment the at least one previous therapy. In some aspects, the at least one previous therapy is continued to be administered to the subject after the administration of therapeutic cells of the present disclosure. [0234] In some aspects, the at least one previous therapy can be selected from surgery, an immunotherapy, a stem cell transplant, an anti-cancer therapy, chemotherapy, targeted drug therapy, radiation therapy, or any combination thereof. In some aspects, the at least one previous therapy is radiation therapy. In some aspects, the at least one previous therapy is chemotherapy. In some aspects, the at least one previous therapy comprises the administration of a combination of venetoclax and azacitidine. [0235] In some aspects, the at least one previous therapy is surgery. In some aspects, the surgery comprises the amputation of one or more body parts. Accordingly, the present disclosure provides methods of preventing cancer metastasis in a subject having Ewing’s sarcoma, wherein the subject previously underwent an amputation of one or more body parts to treat the Ewing’s sarcoma. [0236] As used herein, the term “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of a compound of the present disclosure, or a pharmaceutically acceptable salt, polymorph or solvate thereof, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model. [0237] As used herein, “prevent”, “preventing” and the like describe stopping the onset of the disease, condition or disorder, or one or more symptoms or complications thereof. [0238] The terms “effective amount” and “therapeutically effective amount” of cells, an agent, or a compound are used in the broadest sense to refer to a nontoxic but sufficient amount of the cells, active agent, or compound to provide the desired effect or benefit. [0239] In some aspects, the therapeutic cells of the present disclosure can be administered to the subject in an amount of at least about 0.1x10⁶ cells/kg, or at least about 0.25x10⁶ cells/kg, or at least about 0.5x10⁶ cells/kg, or at least about 0.75x10⁶ cells/kg, or at least about 1x10⁶ cells/kg, or at least about 1.25x10⁶ cells/kg, or at least about 1.5x10⁶ cells/kg, or at least about 1.75x10⁶ cells/kg, or at least about 2x10⁶ cells/kg, or at least about 2.25x10⁶ cells/kg, or at Attorney Docket No.: UNCO-064/001WO 300978-2237 least about 2.5x10⁶ cells/kg, or at least about 2.75x10⁶ cells/kg, or at least about 3x10⁶ cells/kg. [0240] In some aspects, the therapeutic cells of the present disclosure can be administered to the subject in an amount of about 0.1x10⁶ cells/kg, or about 0.25x10⁶ cells/kg, or about 0.5x10⁶ cells/kg, or about 0.75x10⁶ cells/kg, or about 1x10⁶ cells/kg, or about 1.25x10⁶ cells/kg, or about 1.5x10⁶ cells/kg, or about 1.75x10⁶ cells/kg, or about 2x10⁶ cells/kg, or about 2.25x10⁶ cells/kg, or about 2.5x10⁶ cells/kg, or about 2.75x10⁶ cells/kg, or about 3x10⁶ cells/kg. [0241] In some aspects, the therapeutic cells of the present disclosure can be administered in an amount that does not exceed about 5x10⁶ cells, or about 10x10⁶ cells, or about 15x10⁶ cells, or about 20x10⁶ cells, or about 25x10⁶ cells, or about 30x10⁶ cells, or about 35x10⁶ cells, or about 40x10⁶ cells, or about 45x10⁶ cells, or about 50x10⁶ cells, or about 55x10⁶ cells, or about 60x10⁶ cells, or about 65x10⁶ cells, or about 70x10⁶ cells, or about 75x10⁶ cells, or about 80x10⁶ cells, or about 85x10⁶ cells, or about 90x10⁶ cells, or about 95x10⁶ cells, or about 100x10⁶ cells, or about 105x10⁶ cells, or about 110x10⁶, or about 115x10⁶ cells, or about 120x10⁶ cells, or about 125x10⁶ cells, or about 130x10⁶ cells, or about 135x10⁶ cells, or about 140x10⁶ cells, or about 145x10⁶ cells, or about 150x10⁶ cells, or about 155x10⁶ cells, or about 160x10⁶ cells, or about 165x10⁶ cells, or about 170x10⁶ cells, or about 175x10⁶ cells, or about 180x10⁶ cells, or about 185x10⁶ cells, or about 190x10⁶ cells, or about 195x10⁶ cells, or about 200x10⁶ cells, or about 205x10⁶ cells, or about 210x10⁶, or about 215x10⁶ cells, or about 220x10⁶ cells, or about 225x10⁶ cells, or about 230x10⁶ cells, or about 235x10⁶ cells, or about 240x10⁶ cells, or about 245x10⁶ cells, or about 250x10⁶ cells, or about 300x10⁶, or about 350x10⁶, or about 400x10⁶, or about 450x10⁶, or about 500x10⁶, or about 600x10⁶, or about 700x10⁶. [0242] The term "benefit" is used in the broadest sense and refers to any desirable effect and specifically includes clinical benefit as defined herein. Clinical benefit can be measured by assessing various endpoints, e.g., inhibition, to some extent, of disease progression, including slowing down and complete arrest; reduction in the number of disease episodes and/or symptoms; reduction in lesion size; inhibition (i.e., reduction, slowing down or complete stopping) of disease cell infiltration into adjacent peripheral organs and/or tissues; inhibition (i.e. reduction, slowing down or complete stopping) of disease spread; decrease of auto- immune response, which may, but does not have to, result in the regression or ablation of the disease lesion; relief, to some extent, of one or more symptoms associated with the disorder; increase in the length of disease-free presentation following treatment, e.g., progression-free Attorney Docket No.: UNCO-064/001WO 300978-2237 survival; increased overall survival; higher response rate; and/or decreased mortality at a given point of time following treatment. [0243] Methods of Cell Production of the Present Disclosure [0244] The present disclosure provides methods of producing the therapeutic cells and pluralities of therapeutic cells of the present disclosure. [0245] Accordingly, the present disclosure provides a method of producing a plurality of cells expressing the logic pairs of CAR polypeptides of the present disclosure, the method comprising: a) obtaining a plurality of cells from a subject; and b) introducing into the plurality of cells one or more nucleic acid molecules of the present disclosure, wherein the one or more nucleic acid molecules comprise one or more nucleic acid sequences encoding for the logic pair of CAR polypeptides of the present disclosure. [0246] In applications wherein cells are taken from a subject and then eventually transplanted back into the subject therapeutically, these cells are said to be “autologous”. In aspects wherein cells are taken from a first subject and then eventually transplanted into a different, second subject, these cells are said to be “allogeneic”. [0247] The term "introducing" is intended presenting to the cell the nucleic acid molecules in such a manner that the nucleic acid molecule gains access to the interior of the host cell. The methods of the present disclosure do not depend on a particular method for introducing a nucleic acid molecule into a host cell, only that the polynucleotide construct gains access to the interior of one cell of the host. Methods for introducing nucleic acid molecules (e.g. vectors) into bacteria, plants, fungi and animals are known in the art including, but not limited to, stable transformation methods, transient transformation methods, and virus- mediated methods. For example, lentiviral and retroviral transduction methods can be used. As would be appreciated by the skilled artisan, these methods can comprise the use of retronectin to enhance efficiency of transduction. [0248] The methods of cell production described above can further comprise, before step (b), after step (b), or both before step (b) and after step (b), expanding the cells. Cell expansion can be accomplished using any cell expansion method known in the art. [0249] The methods of cell production described above can further comprise, before step (b), after step (b), or both before step (b) and after step (b), culturing the cells. Cell culturing can be accomplished using any cell culturing method known in the art. [0250] The manufacturing methods described above can further comprise, after step (b), enriching for cells that express the logic pair of CAR polypeptides of the present disclosure. The enrichment can be accomplished by contacting the plurality of cells with an affinity Attorney Docket No.: UNCO-064/001WO 300978-2237 reagent that binds to the either of the CAR polypeptides of the logic pair of CAR polypeptides. In some aspects, the affinity reagent is an antibody that binds to one of the CAR polypeptides of the logic pair. In some aspects, following enrichment, at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%, or at least about 97%, or at least about 99%, or at least about 100% of the cells express the logic pair of CAR polypeptides of the present disclosure. [0251] Kits [0252] The present disclosure provides kits comprising any of the compositions described, or any combination of the compositions described herein. [0253] Accordingly, the present disclosure provides kits comprising: i) the anti-CD99 CAR polypeptides of the present disclosure; ii) the anti-CD276 CAR polypeptides of the present disclosure; iii) the logic pairs of CAR polypeptides of the present disclosure; iv) the cells of the present disclosure; v) the cell populations of the present disclosure; vi) the nucleic acid molecules of the present disclosure; or any combination thereof. [0254] General Methods and Definitions [0255] Methods of Gene Delivery and Cell Modification [0256] As used herein, “vector” means a construct, which is capable of delivering, and, in some embodiments, expressing, one or more gene(s) or sequence(s) of interest in a host cell. Examples of vectors include, but are not limited to, viral vectors, naked DNA or RNA expression vectors, plasmid, cosmid or phage vectors, DNA or RNA expression vectors associated with cationic condensing agents, DNA or RNA expression vectors encapsulated in liposomes, and certain eukaryotic cells, such as producer cells. [0257] One of skill in the art would be well-equipped to construct a vector through standard recombinant techniques (see, for example, Sambrook et al., 2001 and Ausubel et al, 1996, both incorporated herein by reference) for the expression of the antigen receptors of the present disclosure. Vectors include but are not limited to, plasmids, cosmids, viruses (bacteriophage, animal viruses, and plant viruses), and artificial chromosomes (e.g., YACs), such as retroviral vectors (e.g. derived from Moloney murine leukemia virus vectors (MoMLV), MSCV, SFFV, MPSV, SNV etc), lentiviral vectors (e.g. derived from HIV-1, HIV-2, SIV, BIV, FIV etc.), adenoviral (Ad) vectors including replication competent, replication deficient and gutless forms thereof, adeno-associated viral (AAV) vectors, simian Attorney Docket No.: UNCO-064/001WO 300978-2237 virus 40 (SV-40) vectors, bovine papilloma virus vectors, Epstein-Barr virus vectors, herpes virus vectors, vaccinia virus vectors, Harvey murine sarcoma virus vectors, murine mammary tumor virus vectors, Rous sarcoma virus vectors, parvovirus vectors, polio virus vectors, vesicular stomatitis virus vectors, maraba virus vectors and group B adenovirus enadenotucirev vectors. [0258] Viral Vectors [0259] Viral vectors encoding an antigen receptor, a cytokine and/or an functional effector element may be provided in certain aspects of the methods of the present disclosure. In generating recombinant viral vectors, non-essential genes are typically replaced with a gene or coding sequence for a heterologous (or non-native) protein. A viral vector is a kind of expression construct that utilizes viral sequences to introduce nucleic acid and possibly proteins into a cell. The ability of certain viruses to infect cells or enter cells via receptor mediated- endocytosis, and to integrate into host cell genomes and express viral genes stably and efficiently have made them attractive candidates for the transfer of foreign nucleic acids into cells (e.g., mammalian cells). Non- limiting examples of virus vectors that may be used to deliver a nucleic acid of certain aspects of the present invention are described below. [0260] In some embodiments of the methods of the disclosure, introducing a nucleic acid sequence and/or a genomic editing construct into an immune cell ex vivo, in vivo, in vitro or in situ comprises a viral vector. In some embodiments, the viral vector is a non-integrating non-chromosomal vector. Exemplary non-integrating non-chromosomal vectors include, but are not limited to, adeno-associated virus (AAV), adenovirus, and herpes viruses. In some embodiments, the viral vector is an integrating chromosomal vector. Integrating chromosomal vectors include, but are not limited to, adeno-associated vectors (AAV), Lentiviruses, and gamma-retroviruses. [0261] In some embodiments of the methods of the disclosure, introducing a nucleic acid sequence and/or a genomic editing construct into an immune cell ex vivo, in vivo, in vitro or in situ comprises a combination of vectors. Exemplary, non-limiting vector combinations include: viral and non-viral vectors, a plurality of non-viral vectors, or a plurality of viral vectors. Exemplary but non-limiting vectors combinations include: a combination of a DNA- derived and an RNA-derived vector, a combination of an RNA and a reverse transcriptase, a combination of a transposon and a transposase, a combination of a non-viral vector and an endonuclease, and a combination of a viral vector and an endonuclease. [0262] In some embodiments of the methods of the disclosure, genome modification comprising introducing a nucleic acid sequence and/or a genomic editing construct into an Attorney Docket No.: UNCO-064/001WO 300978-2237 immune cell ex vivo, in vivo, in vitro or in situ stably integrates a nucleic acid sequence, transiently integrates a nucleic acid sequence, produces site-specific integration a nucleic acid sequence, or produces a biased integration of a nucleic acid sequence. In some embodiments, the nucleic acid sequence is a transgene. [0263] In some embodiments of the methods of the disclosure, genome modification comprising introducing a nucleic acid sequence and/or a genomic editing construct into an immune cell ex vivo, in vivo, in vitro or in situ stably integrates a nucleic acid sequence. In some embodiments, the stable chromosomal integration can be a random integration, a site- specific integration, or a biased integration. In some embodiments, the site-specific integration can be non-assisted or assisted. In some embodiments, the assisted site-specific integration is co-delivered with a site-directed nuclease. In some embodiments, the site- directed nuclease comprises a transgene with 5’ and 3’ nucleotide sequence extensions that contain a percentage homology to upstream and downstream regions of the site of genomic integration. In some embodiments, the transgene with homologous nucleotide extensions enable genomic integration by homologous recombination, microhomology-mediated end joining, or nonhomologous end-joining. In some embodiments the site-specific integration occurs at a safe harbor site. Genomic safe harbor sites are able to accommodate the integration of new genetic material in a manner that ensures that the newly inserted genetic elements function reliably (for example, are expressed at a therapeutically effective level of expression) and do not cause deleterious alterations to the host genome that cause a risk to the host organism. Potential genomic safe harbors include, but are not limited to, intronic sequences of the human albumin gene, the adeno-associated virus site 1 (AAVS1), a naturally occurring site of integration of AAV virus on chromosome 19, the site of the chemokine (C-C motif) receptor 5 (CCR5) gene and the site of the human ortholog of the mouse Rosa26 locus. [0264] In some embodiments, the site-specific transgene integration occurs at a site that disrupts expression of a target gene. In some embodiments, disruption of target gene expression occurs by site-specific integration at introns, exons, promoters, genetic elements, enhancers, suppressors, start codons, stop codons, and response elements. In some embodiments, exemplary target genes targeted by site-specific integration include but are not limited to any immunosuppressive gene, and genes involved in allo-rejection. [0265] In some embodiments, the site-specific transgene integration occurs at a site that results in enhanced expression of a target gene. In some embodiments, enhancement of target gene expression occurs by site-specific integration at introns, exons, promoters, genetic elements, enhancers, suppressors, start codons, stop codons, and response elements. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0266] Regulatory Elements [0267] Expression cassettes included in vectors useful in the present disclosure in particular contain (in a 5'-to-3' direction) a eukaryotic transcriptional promoter operably linked to a protein-coding sequence, splice signals including intervening sequences, and a transcriptional termination/polyadenylation sequence. The promoters and enhancers that control the transcription of protein encoding genes in eukaryotic cells are composed of multiple genetic elements. The cellular machinery is able to gather and integrate the regulatory information conveyed by each element, allowing different genes to evolve distinct, often complex patterns of transcriptional regulation. A promoter used in the context of the present disclosure includes constitutive, inducible, and tissue-specific promoters. [0268] Origins of Replication [0269] In order to propagate a vector in a host cell, it may contain one or more origins of replication sites (often termed "ori"), for example, a nucleic acid sequence corresponding to oriP of EBV as described above or a genetically engineered oriP with a similar or elevated function in programming, which is a specific nucleic acid sequence at which replication is initiated. Alternatively, a replication origin of other extra-chromosomally replicating virus as described above or an autonomously replicating sequence (ARS) can be employed. [0270] Other Methods of Nucleic Acid Delivery [0271] In addition to viral delivery of the nucleic acids encoding the antigen receptor, the following are additional methods of recombinant gene delivery to a given cell, (e.g. an NK cell) and are thus considered in the present disclosure. [0272] Introduction of a nucleic acid molecule, such as DNA or RNA, into the immune cells of the current disclosure may use any suitable methods for nucleic acid delivery for transformation of a cell, as described herein or as would be known to one of ordinary skill in the art. Such methods include, but are not limited to, direct delivery of DNA such as by ex vivo transfection, by injection, including microinjection); by electroporation; by calcium phosphate precipitation; by using DEAE-dextran followed by polyethylene glycol; by direct sonic loading; by liposome mediated transfection and receptor-mediated transfection; by lipid nanoparticle transfection; by microprojectile bombardment; by agitation with silicon carbide fibers; by Agrobacterium-mediated transformation; by desiccation/inhibition-mediated DNA uptake, and any combination of such methods. Through the application of techniques such as these, organelle(s), cell(s), tissue(s) or organism(s) may be stably or transiently transformed. [0273] Generally, the gene transfer system can include a transposon-based or a viral-based integration system. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0274] In some embodiments, the gene transfer system comprises a transposon system. DNA transposons can translocate via a non-replicative “cut-and-paste” mechanism. This mechanism requires recognition of the two inverse terminal repeats (ITRs) by a catalytic enzyme, i.e., transposase, which can cleave its target and consequently release the DNA transposon from its donor template. Upon excision, the DNA transposons may subsequently integrate into the acceptor DNA that is cleaved by the same transposase. In some of their natural configurations, DNA transposons are flanked by two ITRs and may contain a gene encoding a transposase that catalyzes transposition. As would be appreciated by the skilled artisan, transposon systems offer many advantages for nucleic acid integration, e.g., as compared to viral vectors. For example, transposons can carry larger cargos, which can be advantageous for delivering one or more of the CARs, functional effector elements, and/or cytokines disclosed herein, to an immune cell (e.g., an NK cell). Further, transposons may comprise, for example, CRISPR tools (e.g., along with cargo), and thereby allow multiplex engineering of a cell. [0275] Chimeric Antigen Receptors [0276] A "chimeric antigen receptor" is also known as an artificial cell receptor, a chimeric cell receptor, or a chimeric immunoreceptor. As would be appreciated by the skilled artisan, Chimeric antigen receptors (CARs) are engineered receptors, which graft a selected specificity onto an immune effector cell. CARs typically have an extracellular domain (ectodomain), a transmembrane domain and an intracellular (endodomain) domain. In some embodiments, the ectodomain comprises an antigen-binding domain and a hinge domain, wherein the antigen-binding domain specifically binds to an antigen that is of particular interest in the treatment of a specific disease or disorder (e.g. an antigen that is located on particular cancer cells or an antigen located on an infected cell). In some embodiments, the antigen is a protein expressed on the surface of cells (e.g., on the surface of a cancer cell, or an infected cell). [0277] As would be appreciated by the skilled artisan, CARs are available in various different “formats”, sometimes also referred to as different “generations” of CARs (see e.g. Hiltensperger M, Krackhardt AM. Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells. Front Immunol.2023 Mar 6;14:1121030. doi: 10.3389/fimmu.2023.1121030. PMID: 36949949; PMCID: PMC10025359). Accordingly, the term engineered CAR as used herein encompasses any of the formats/generations known in the art. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0278] In a non-limiting example, the CAR can be in the format of a universal CAR, such as those disclosed in PCT Publication No. WO/2012/082841 and US Patent Nos.9,233,125 and 10,973,893. As would be appreciated by the skilled artisan, in universal CAR systems, the extracellular domain of the CAR specifically binds to a common “tag” molecule. Such CARs can be referred to as “anti-tag CARs”. These tag molecules can then be fused to antigen- targeting molecules (e.g. antibodies), such that the anti-tag CARs bind to a target cell of interest indirectly through the tag-fusion protein. In this way, subjects can be administered a single population of cells expressing an anti-tag CAR and then a variety of different tag- fusion proteins that can specifically directed the anti-tag CAR cells to target different cells. [0279] Engineered T cell Receptors [0280] As would be appreciated by the skilled artisan, a T cell Receptor (TCR) is a heterodimeric cell surface protein of the immunoglobulin super-family, which is associated with invariant proteins of the CD3 complex involved in mediating signal transduction. TCRs exist as Įȕ and Ȗį heterodimers, which are structurally similar but have quite distinct anatomical locations and probably functions. The extracellular portion of native heterodimeric PTCR consists of two polypeptide chains, each of which has a membrane- proximal constant domain, and a membrane-distal variable domain. Each of the constant and variable domains includes an intra-chain disulfide bond. The variable domains contain the highly polymorphic loops analogous to the complementarity determining regions (CDRs) of antibodies. As used herein, the term “engineered T cell receptor” refers to TCRs that have been designed to specifically bind to an antigen that is of particular interest in the treatment of a specific disease or disorder (e.g. an antigen that is located on particular cancer cells or an antigen located on an infected cell). In some embodiments, the antigen is a protein expressed on the surface of cells (e.g., on the surface of a cancer cell, or an infected cell). As would be appreciated by the skilled artisan, engineered TCRs are available in various different “formats” (see e.g. Hiltensperger M, Krackhardt AM. Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells. Front Immunol.2023 Mar 6;14:1121030. doi: 10.3389/fimmu.2023.1121030. PMID: 36949949; PMCID: PMC10025359). Accordingly, the term engineered TCR as used herein encompasses any of the formats known in the art. [0281] Definitions [0282] As would be appreciated by the skilled artisan, “CD99” refers to the protein known as cluster of differentiation 99, which is also referred to in the art as MIC2. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0283] As would be appreciated by the skilled artisan, “CD276” refers to the protein known as cluster of differentiation 276, which is also referred to in the art as B7 Homolog 3 (B7- H3). [0284] As used herein, the term "antigen" is a molecule capable of being bound by an antibody, T cell receptor, Chimeric Antigen Receptor and or engineered immune receptor. An antigen may generally be used to induce a humoral immune response and/or a cellular immune response leading to the production of B and/or T lymphocytes. [0285] The terms "tumor-associated antigen," "tumor antigen" and "cancer cell antigen" are used interchangeably herein. In each case, the terms refer to proteins, glycoproteins or carbohydrates that are specifically or preferentially expressed by cancer cells. [0286] As used herein, the term “portion” when used in reference to a polypeptide or a peptide refers to a fragment of the polypeptide or peptide. In some embodiments, a “portion” of a polypeptide or peptide retains at least one function and/or activity of the full-length polypeptide or peptide from which it was derived. For example, in some embodiments, if a full-length polypeptide binds a given ligand, a portion of that full-length polypeptide also binds to the same ligand. [0287] The terms “protein” and “polypeptide” are used interchangeably herein. [0288] As known in the art, “nucleic acid molecule,” “polynucleotide,” or “nucleic acid,” as [0289] The term "exogenous," when used in relation to a protein, gene, nucleic acid, or polynucleotide in a cell or organism refers to a protein, gene, nucleic acid, or polynucleotide that has been introduced into the cell or organism by artificial or natural means; or in relation to a cell, the term refers to a cell that was isolated and subsequently introduced into a cell population or to an organism by artificial or natural means. An exogenous nucleic acid may be from a different organism or cell, or it may be one or more additional copies of a nucleic acid that occurs naturally within the organism or cell. An exogenous cell may be from a different organism, or it may be from the same organism. By way of a non-limiting example, an exogenous nucleic acid is one that is in a chromosomal location different from where it Attorney Docket No.: UNCO-064/001WO 300978-2237 would be in natural cells, or is otherwise flanked by a different nucleic acid sequence than that found in nature. The term “exogenous” is used interchangeably with the term “heterologous”. [0290] By "expression construct" or "expression cassette" is used to mean a nucleic acid molecule that is capable of directing transcription. An expression construct includes, at a minimum, one or more transcriptional control elements (such as promoters, enhancers or a structure functionally equivalent thereof) that direct gene expression in one or more desired cell types, tissues or organs. Additional elements, such as a transcription termination signal, may also be included. [0291] A "gene," "polynucleotide," "coding region," "sequence," "nucleic acid sequence," "segment," "fragment," or "transgene" that "encodes" a particular protein, is a section of a nucleic acid molecule that is transcribed and optionally also translated into a gene product, e.g., a polypeptide, in vitro or in vivo when placed under the control of appropriate regulatory sequences. The coding region may be present in either a cDNA, genomic DNA, or RNA form. When present in a DNA form, the nucleic acid molecule may be single-stranded (i.e., the sense strand) or double-stranded. The boundaries of a coding region are determined by a start codon at the 5' (amino) terminus and a translation stop codon at the 3' (carboxy) terminus. A gene can include, but is not limited to, cDNA from prokaryotic or eukaryotic mRNA, genomic DNA sequences from prokaryotic or eukaryotic DNA, and synthetic DNA sequences. A transcription termination sequence will usually be located 3' to the gene sequence. [0292] The term "cell" is herein used in its broadest sense in the art and refers to a living body that is a structural unit of tissue of a multicellular organism, is surrounded by a membrane structure that isolates it from the outside, has the capability of self-replicating, and has genetic information and a mechanism for expressing it. Cells used herein may be naturally-occurring cells or artificially modified cells (e.g., fusion cells, genetically modified cells, etc.). [0293] "Antibody" as used herein refers to monoclonal or polyclonal antibodies. The term "monoclonal antibodies," as used herein, refers to antibodies that are produced by a single clone of B-cells and bind to the same epitope. In contrast, "polyclonal antibodies" refer to a population of antibodies that are produced by different B-cells and bind to different epitopes of the same antigen. A whole antibody typically consists of four polypeptides: two identical copies of a heavy (H) chain polypeptide and two identical copies of a light (L) chain polypeptide. Each of the heavy chains contains one N-terminal variable (VH) region and Attorney Docket No.: UNCO-064/001WO 300978-2237 three C-terminal constant (CHL CH2 and CH3) regions, and each light chain contains one N- terminal variable (VL) region and one C-terminal constant (CL) region. The variable regions of each pair of light and heavy chains form the antigen binding site of an antibody. The VH and VL regions have a similar general structure, with each region comprising four framework regions, whose sequences are relatively conserved. The framework regions are connected by three complementarity determining regions (CDRs). The three CDRs, known as CDR1, CDR2, and CDR3, form the "hypervariable region" of an antibody, which is responsible for antigen binding. [0294] The term "T cell" refers to T lymphocytes, and includes, but is not limited to, Ȗ/į T cells, Į/ȕ T cells, NK T cells, CD4⁺ T cells and CD8⁺ T cells. CD4⁺ T cells include THO, T_h1 and TH2 cells, as well as regulatory T cells (Treg). There are at least three types of regulatory T cells: CD4⁺ CD25⁺ Treg, CD25 TH3 Treg, and CD25 TR 1 Treg. "Cytotoxic T cell" refers to a T cell that can kill another cell. The majority of cytotoxic T cells are CD8⁺ MHC class I- restricted T cells, however some cytotoxic T cells are CD4⁺. In some embodiments, the T cell of the present disclosure is CD4⁺ or CD8⁺. [0295] The activation state of a T cell defines whether the T cell is "resting" (i.e., in the Go phase of the cell cycle) or "activated" to proliferate after an appropriate stimulus such as the recognition of its specific antigen, or by stimulation with OKT3 antibody, PHA or PMA, etc. The "phenotype" of the T cell (e.g., naive, central memory, effector memory, lytic effectors, help effectors (THI and TH2 cells), and regulatory effectors), describes the function the cell exerts when activated. A healthy donor has T cells of each of these phenotypes, and which are predominately in the resting state. A naive T cell will proliferate upon activation, and then differentiate into a memory T cell or an effector T cell. It can then assume the resting state again, until it gets activated the next time, to exert its new function and may change its phenotype again. An effector T cell will divide upon activation and antigen- specific effector function. [0296] "Natural killer T cells" (NKT cells), not to be confused with natural killer cells of the innate immune system, bridge the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigens presented by major histocompatibility complex (WIC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e., cytokine production and release of cytolytic/cell killing molecules). They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0297] “Natural killer cells” (“NK cells”) are a type of cytotoxic lymphocyte of the innate immune system. In some instances, NK cells provide a first line defense against viral infections and/or tumor formation. NK cells can detect MHC presented on infected or cancerous cells, triggering cytokine release, and subsequently induce lysis and apoptosis. NK cells can further detect stressed cells in the absence of antibodies and/or MHC, thereby allowing a rapid immune response. [0298] The term "culturing" refers to the in vitro maintenance, differentiation, and/or propagation of cells in suitable media. By "enriched" is meant a composition comprising cells present in a greater percentage of total cells than is found in the tissues where they are present in an organism. [0299] As used throughout the disclosure, identity between two sequences may be determined by using the stand-alone executable BLAST engine program for blasting two sequences (bl2seq), which can be retrieved from the National Center for Biotechnology Information (NCBI) ftp site, using the default parameters (Tatusova and Madden, FEMS Microbiol Lett., 1999, 174, 247-250; which is incorporated herein by reference in its entirety). The terms "identical" or "identity" when used in the context of two or more nucleic acids or polypeptide sequences, refer to a specified percentage of residues that are the same over a specified region of each of the sequences. In some embodiments, the sequence identify is determined over the entire length of a sequence. The percentage can be calculated by optimally aligning the two sequences, comparing the two sequences over the specified region, determining the number of positions at which the identical residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the specified region, and multiplying the result by 100 to yield the percentage of sequence identity. In cases where the two sequences are of different lengths or the alignment produces one or more staggered ends and the specified region of comparison includes only a single sequence, the residues of single sequence are included in the denominator but not the numerator of the calculation. When comparing DNA and RNA, thymine (T) and uracil (U) can be considered equivalent. Identity can be performed manually or by using a computer sequence algorithm such as BLAST or BLAST 2.0. [0300] Exemplary Embodiments [0301] Embodiment 1. An anti-CD276 CAR polypeptide comprising from N-terminus to C- terminus, an anti-CD276 antigen binding domain, a transmembrane domain and at least one costimulatory domain. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0302] Embodiment 2. An anti-CD276 CAR polypeptide comprising from N-terminus to C- terminus, an anti-CD276 antigen binding domain, a transmembrane domain and at least one activation domain. [0303] Embodiment 3. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide further comprises a hinge domain located between the anti-CD276 antigen binding domain and the transmembrane domain. [0304] Embodiment 4. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide further comprises a signal peptide at the N-terminus. [0305] Embodiment 5. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 antigen binding domain comprises an anti-CD276 scFv. [0306] Embodiment 6. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 antigen binding domain comprises a CDHR1 having the amino acid sequence of SEQ ID NO: 1, a CDRH2 having the amino acid sequence of SEQ ID NO: 2, a CDRH3 having the amino acid sequence of SEQ ID NO: 3, a CDRL1 having the amino acid sequence of SEQ ID NO: 4, a CDRL2 having the amino acid sequence of SEQ ID NO: 5, a CDHL3 having the amino acid sequence of SEQ ID NO: 6. [0307] Embodiment 7. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 antigen binding domain comprises the amino acid sequence of SEQ ID NO: 12. [0308] Embodiment 8. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the transmembrane domain comprises a CD8 transmembrane domain. [0309] Embodiment 9. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the CD8 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 46. [0310] Embodiment 10. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the transmembrane domain comprises a CD28 transmembrane domain. [0311] Embodiment 11. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the CD28 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 44. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0312] Embodiment 12. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the at least one costimulatory domain comprises at least one 4-1BB costimulatory polypeptide. [0313] Embodiment 13. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the at least one 4-1BB costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 50. [0314] Embodiment 14. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the at least one costimulatory domain comprises at least one CD28 costimulatory polypeptide. [0315] Embodiment 15. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the at least one CD28 costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 48. [0316] Embodiment 16. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the signal peptide comprises a CD8 signal peptide. [0317] Embodiment 17. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the CD8 signal peptide comprises the amino acid sequence of SEQ ID NO: 56. [0318] Embodiment 18. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the signal peptide comprises a GMCSF signal peptide. [0319] Embodiment 19. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the GMCSF signal peptide comprises the amino acid sequence of SEQ ID NO: 58. [0320] Embodiment 20. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the hinge domain comprises a CD8 hinge domain [0321] Embodiment 21. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the CD8 hinge domain comprises the amino acid sequence of SEQ ID NO: 42. [0322] Embodiment 22. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the hinge domain comprises a CD28 hinge domain. [0323] Embodiment 23. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the CD28 hinge domain comprises the amino acid sequence of SEQ ID NO: 40. [0324] Embodiment 24. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the activation domain comprises a CD3ȗ activation polypeptide. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0325] Embodiment 25. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the CD3ȗ activation polypeptide comprises the amino acid sequence of SEQ ID NO: 52. [0326] Embodiment 26. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C- terminus, a signal peptide comprising a GMSCF signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, a hinge domain comprising a CD28 hinge polypeptide, a transmembrane domain comprising a CD28 transmembrane polypeptide, and at least one costimulatory domain comprising at least one CD28 costimulatory polypeptide. [0327] Embodiment 27. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide comprises the amino acid sequence of SEQ ID NO: 63. [0328] Embodiment 28. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C- terminus, a signal peptide comprising a GMCSF signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and at least one costimulatory domain comprising at least one 4-1BB costimulatory polypeptide. [0329] Embodiment 29. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide comprises the amino acid sequence of SEQ ID NO: 64. [0330] Embodiment 30. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C- terminus, a signal peptide comprising a GMCSF signal peptide, an anti-CD276 antigen binding domain comprising an anti-CD276 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and at least one activation domain comprising at least one CD3ȗ activation polypeptide. [0331] Embodiment 31. The anti-CD276 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD276 CAR polypeptide comprises the amino acid sequence of SEQ ID NO: 62. [0332] Embodiment 32. An anti-CD99 CAR polypeptide comprising from N-terminus to C- terminus, an anti-CD99 antigen binding domain, a transmembrane domain and an activation domain. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0333] Embodiment 33. An anti-CD99 CAR polypeptide comprising from N-terminus to C- terminus, an anti-CD99 antigen binding domain, a transmembrane domain and a costimulatory domain. [0334] Embodiment 34. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide further comprises a hinge domain located between the anti-CD99 antigen binding domain and the transmembrane domain. [0335] Embodiment 35. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide further comprises a signal peptide at the N-terminus. [0336] Embodiment 36. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 antigen binding domain comprises an anti-CD99 scFv. [0337] Embodiment 37. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 antigen binding domain comprises a CDHR1 having the amino acid sequence of SEQ ID NO: 27, a CDRH2 having the amino acid sequence of SEQ ID NO: 28, a CDRH3 having the amino acid sequence of SEQ ID NO: 29, a CDRL1 having the amino acid sequence of SEQ ID NO: 30, a CDRL2 having the amino acid sequence of SEQ ID NO: 31, a CDHL3 having the amino acid sequence of SEQ ID NO: 32. [0338] Embodiment 38. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 antigen binding domain comprises the amino acid sequence of SEQ ID NO: 38. [0339] Embodiment 39. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the transmembrane domain comprises a CD8 transmembrane domain. [0340] Embodiment 40. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the CD8 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 46. [0341] Embodiment 41. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the transmembrane domain comprises a CD28 transmembrane domain. [0342] Embodiment 42. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the CD28 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 44. [0343] Embodiment 43. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the activation domain comprises a CD3ȗ activation polypeptide. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0344] Embodiment 44. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the CD3ȗ activation polypeptide comprises the amino acid sequence of SEQ ID NO: 52. [0345] Embodiment 45. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the at least one costimulatory domain comprises at least one 4-1BB costimulatory polypeptide. [0346] Embodiment 46. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the at least one 4-1BB costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 50. [0347] Embodiment 47. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the at least one costimulatory domain comprises at least one CD28 costimulatory polypeptide. [0348] Embodiment 48. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the at least one CD28 costimulatory polypeptide comprises the amino acid sequence of SEQ ID NO: 48. [0349] Embodiment 49. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the signal peptide comprises a CD8 signal peptide. [0350] Embodiment 50. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the CD8 signal peptide comprises the amino acid sequence of SEQ ID NO: 56. [0351] Embodiment 51. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the signal peptide comprises a GMCSF signal peptide. [0352] Embodiment 52. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the GMCSF signal peptide comprises the amino acid sequence of SEQ ID NO: 58. [0353] Embodiment 53. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the hinge domain comprises a CD8 hinge domain. [0354] Embodiment 54. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the CD8 hinge domain comprises the amino acid sequence of SEQ ID NO: 42. [0355] Embodiment 55. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the hinge domain comprises a CD28 hinge domain. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0356] Embodiment 56. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the CD28 hinge domain comprises the amino acid sequence of SEQ ID NO: 40. [0357] Embodiment 57. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C- terminus, a signal peptide comprising a CD8 signal peptide, an anti-CD99 antigen binding domain comprising an anti-CD276 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and an activation domain comprising a CD3ȗ activation polypeptide. [0358] Embodiment 58. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide comprises the amino acid sequence of SEQ ID NO: 65. [0359] Embodiment 59. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C- terminus, a signal peptide comprising a CD8 signal peptide, an anti-CD99 antigen binding domain comprising an anti-CD99 scFv, a hinge domain comprising a CD28 hinge polypeptide, a transmembrane domain comprising a CD28 transmembrane polypeptide, and at least one costimulatory domain comprising at least one CD28 costimulatory polypeptide. [0360] Embodiment 60. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide comprises the amino acid sequence of SEQ ID NO: 61. [0361] Embodiment 61. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C- terminus, a signal peptide comprising a GMCSF signal peptide, an anti-CD99 antigen binding domain comprising an anti-CD99 scFv, a hinge domain comprising a CD8 hinge polypeptide, a transmembrane domain comprising a CD8 transmembrane polypeptide, and at least one costimulatory domain comprising at least one 4-1BB costimulatory polypeptide. [0362] Embodiment 62. The anti-CD99 CAR polypeptide of any one of the preceding embodiments, wherein the anti-CD99 CAR polypeptide comprises the amino acid sequence of SEQ ID NO: 60. [0363] Embodiment 63. A logic pair of CAR polypeptides, wherein the logic pair of CAR polypeptides comprises: i) the anti-CD276 CAR polypeptide of any one of the preceding embodiments; and ii) the anti-CD99 CAR polypeptide of any one of the preceding embodiments. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0364] Embodiment 64. A nucleic acid molecule comprising one or more nucleic acid sequences encoding for the anti-CD276 CAR polypeptide of any one of the preceding embodiments. [0365] Embodiment 65. A nucleic acid molecule comprising one or more nucleic acid sequences encoding for the anti-CD99 CAR polypeptide of any one of the preceding embodiments. [0366] Embodiment 66. A nucleic acid molecule comprising: i) one or more nucleic acid sequences encoding for the anti-CD276 CAR polypeptide of any one of the preceding embodiments; and ii) one or more nucleic acid sequences encoding for the anti-CD99 CAR polypeptide of any one of the preceding embodiments. [0367] Embodiment 67. The nucleic acid molecule of any one of the preceding embodiments, wherein the one or more nucleic acid sequences encoding for the anti-CD276 CAR polypeptide and the one or more nucleic acid sequences encoding for the anti-CD99 CAR polypeptide are separated by a nucleic acid sequence encoding for a self-cleaving peptide. [0368] Embodiment 68. The nucleic acid molecule of any one of the preceding embodiments, wherein the self-cleaving peptide is a P2A peptide. [0369] Embodiment 69. The nucleic acid molecule of any one of the preceding embodiments, wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO: 67. [0370] Embodiment 70. The nucleic acid molecule of any one of the preceding embodiments, wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO: 69. [0371] Embodiment 71. The nucleic acid molecule of any one of the preceding embodiments, wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO: 71. [0372] Embodiment 72. The nucleic acid molecule of any one of the preceding embodiments, wherein the nucleic acid molecule comprises the nucleic acid sequence of SEQ ID NO: 73. [0373] Embodiment 73. A vector comprising the nucleic acid molecule of any one of the preceding embodiments. [0374] Embodiment 74. The vector of any one of the preceding embodiments, wherein the vector is a viral vector. [0375] Embodiment 75. The vector of any one of the preceding embodiments, wherein the viral vector is an AAV vector or a lentiviral vector. [0376] Embodiment 76. A cell expressing the anti-CD276 CAR polypeptide of any one of the preceding embodiments and the anti-CD99 CAR polypeptide of any one of the preceding embodiments. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0377] Embodiment 77. A cell expressing the logic pair of CAR polypeptides of any one of the preceding embodiments. [0378] Embodiment 78. The cell of any one of the preceding embodiments, wherein the cell is an immune cell. [0379] Embodiment 79. The cell of any one of the preceding embodiments, wherein the immune cell is a T cell, NK cell, NK-like cell, NKT cell, or cytokine induced killer (CIK) cell. [0380] Embodiment 80. The cell of any one of the preceding embodiments, wherein the immune cell is a T cell. [0381] Embodiment 81. A population of the cells of any one of the preceding embodiments. [0382] Embodiment 82a. A method of treating cancer in a subject, the method comprising administering to the subject one or more amounts of the cell population of any one of the preceding embodiments. [0383] Embodiment 82b. A method of preventing cancer metastasis in a subject, the method comprising administering to the subject one or more amounts of the cell population of any one of the preceding embodiments. [0384] Embodiment 83. The method of any one of the preceding embodiments, the method further comprising administering to the subject at least one additional therapy. [0385] Embodiment 84. The method of any one of the preceding embodiments, wherein the at least one additional therapy comprises radiation therapy. [0386] Embodiment 85. The method of any one of the preceding embodiments, wherein the at least one additional therapy comprises chemotherapy. [0387] Embodiment 86. The method of any one of the preceding embodiments, wherein the at least one additional therapy comprises surgery. [0388] Embodiment 87. The method of any one of the preceding embodiments, wherein the cancer is characterized by expression of both CD99 and CD276 in the cancerous cells. [0389] Embodiment 88. The method of any one of the preceding embodiments, wherein the cancer is diffuse intrinsic pontine glioma. [0390] Embodiment 89. The method of any one of the preceding embodiments, wherein the cancer is acute myeloid leukemia. [0391] Embodiment 90. The method of any one of the preceding embodiments, wherein the cancer is Ewing Sarcoma. [0392] Embodiment 91. The method of any one of the preceding embodiments, wherein the cancer is posterior fossa type A (PFA) ependymoma. Attorney Docket No.: UNCO-064/001WO 300978-2237 [0393] Embodiment 92. The method of any one of the preceding embodiments, wherein the cancer is an atypical teratoid/rhabdoid tumor (ATRT). [0394] Embodiment 93. The method of any one of the preceding embodiments, wherein the cancer is an NK/T-cell lymphoma. [0395] Embodiment 94. The method of any one of the preceding embodiments, wherein the cancer is a large granular lymphocyte leukemia. [0396] Embodiment 95. The method of any one of the preceding embodiments, wherein the cancer is a chronic myeloid leukemia [0397] Embodiment 96. The method of any one of the preceding embodiments, wherein the cancer is a glioblastoma. [0398] Embodiment 97. The method of any one of the preceding embodiments, wherein the cancer is a glioma. [0399] Embodiment 98. The method of any one of the preceding embodiments, wherein the cancer is an ependymoma. [0400] Embodiment 99. The method of any one of the preceding embodiments, wherein the cancer is a neuroblastoma. [0401] Embodiment 100. The method of any one of the preceding embodiments, wherein the cancer is glioblastoma multiforme. [0402] Embodiment 101. The method of any one of the preceding embodiments, wherein the cancer is recurrent cancer. [0403] Embodiment 102. The method of any one of the preceding embodiments, wherein the cancer is refractory cancer. [0404] Embodiment 103. The method of any one of the preceding embodiments, wherein the cancer has metastasized. [0405] Embodiment 104. The method of any one of the preceding embodiments, wherein the subject has been previously administered at least one previous therapy. [0406] Embodiment 105. The method of any one of the preceding embodiments, wherein the at least one previous therapy comprises radiation therapy. [0407] Embodiment 106. The method of any one of the preceding embodiments, wherein the at least one previous therapy comprises chemotherapy. [0408] Embodiment 107. The method of any one of the preceding embodiments, wherein the at least one previous therapy comprises surgery. [0409] Embodiment 108. The method of any one of the preceding embodiments, wherein the surgery comprises amputation of one or more body parts. Attorney Docket No.: UNCO-064/001WO 300978-2237 EXAMPLES [0410] Example 1. Engineering of dual-antigen CARs to improve efficacy and safety. [0411] The following experimental example tests the engineering of dual-antigen chimeric antigen receptors (CARs) by designing CAR-T cells so that only binding to both antigens on the same cell will lead to full activation of the CAR (FIG.1A). Two logic pairs of CARs were designed, “AND CAR-T-1” (which incorporates the 4-1BB costimulatory domain) and “AND CAR-T-2” (which incorporates the CD28 costimulatory domain), using the anti-CD99 and anti-CD276 scFvs described herein (see FIG.1B). [0412] More specifically, the logic pair AND CAR T-1 included an anti-CD99 CAR corresponding to SEQ ID NO: 60 and an anti-CD276 CAR corresponding to SEQ ID NO: 62. The logic pair AND CAR T-2 included an anti-CD99 CAR corresponding to SEQ ID NO: 61 and an anti-CD276 CAR corresponding to SEQ ID NO: 62. [0413] Applicants tested the specificity of the CD99/CD276 logic gated CAR in only targeting cells that express both CD99 and CD276 on their surface and found that both constructs of the CD99/CD276 logic gated CARs protected the single-antigen expressing T cells (CD99+ only) and inhibited T cell fratricide. Cytokine secretion was present in T cells expressing CD99 only when treated with CD99-BBz CAR-T cells at a 1:5 (tumor cell: CAR- T cell) ratio, and not when treated with mock CAR-T cells, anti-CD276 CAR-T cells, or with either CD99/CD276 logic gated CAR-T cells (FIG.2). T cells transduced with either of the AND CAR T-1 logic pair or the AND CAR T-2 logic pair showed an increase in viability compared to T cells transduced with CD99-BBz CARs, indicating the CD99/CD276 logic gated CARs rescue T cells from fratricide (FIG.3). [0414] Example 2. Functionality of single antigen CD99 and CD276 CAR-T cells against DIPG. [0415] The following experimental example tests the functionality of single antigen CD99 and CD276 CAR-T cells against DIPG. Applicants testED protein expression of CD99 and CD276 in DIPG patient tumors and cell lines and found that CD99 and CD276 are highly expressed on DIPG cells (FIGs.3A-3B). [0416] Applicants tested the functionality of single antigen CD99 CAR-T cells or CD276 CAR-T cells against DIPG007 or DIPG BT245 cells. DIPG007 cells were treated with single antigen anti-CD99 CAR-T cells or single antigen anti-CD19 CAR-T cell (mock) at a 1:1 (tumor cell: CAR-T cell) ratio or single antigen anti-CD276 CAR-T cells at a 1:2 (tumor cell: CAR-T cell) ratio and changes in growth were measured using XCELLigence RTCA system to monitor complete tumor lysis. This analysis is shown in FIG.4A. Cytokine Attorney Docket No.: UNCO-064/001WO 300978-2237 production was increased when DIPG007 cells were treated with single antigen anti-CD99 CAR-T cells at a 1:1 ratio and single antigen anti-CD276 CAR-T cells at a 1:2 ratio, as compared to DIPG007 cells treated with single antigen CD19 CAR-T cells (FIG.4B). Cytokine production was also increased when DIPG BT245 tumor cells were treated with single antigen anti-CD99 CAR-T cells at a 1:1 ratio and single antigen anti-CD276 CAR-T cells at a 1:2 ratio, as compared to BT245 cells treated with single antigen anti-CD19 CAR-T cells (FIG.4C). [0417] In a subsequence experiment, a DIPG xenograft model was generated by transplanting BT245 tumor cells into the pons of mice. These mice were then administered single doses (20 million cells) of the single-antigen anti-CD99 CAR-T cells or anti-CD19 CAR-T cells described above. In vivo bioluminescence imaging (IVIS) the xenografts) revealed that while the anti-CD99 CAR-T cells initially cleared DIPG tumors (by 9 days post treatment), the tumors eventually recured (by 42 days post treatment). [0418] Without wishing to be bound by theory, the results presented in this example demonstrate that DIPG tumor cells express both CD99 and CD276 at higher levels than other normal cells, but neither alone is a tumor-specific antigen. Moreover, the targeting of only CD99 using a single antigen CAR-T cell therapy results in eventual relapse of DIPG. [0419] Example 3. Functionality and specificity of CD99/CD276 logic gated CAR-T cells against DIPG. [0420] The following experimental example tests the functionality and specificity of anti- CD99/anti-CD276 CAR logic pairs of the present disclosure for use in treating DIPG. [0421] Applicants tested the anti-tumor efficacy of the AND CAR T-1 logic pair and the AND CAR T-2 logic pair described in Example 1. DIPG007 tumor cells were treated with either T-cells expressing one of the logic pairs at a 1:2 (tumor cell: CAR-T cell) ratio. Changes in growth were measured using XCELLigence real-time measurements. As shown in FIG.5A, this analysis revealed that both of the logic pairs resulted in complete tumor lysis. Moreover, cytokine production was increased when DIPG007 cells were treated with either of the two different logic pairs at a 1:2 ratio (tumor cell: CAR-T cell) ratio, as compared to DIPG007 cells treated with single antigen anti-CD19 CAR-T cells (FIG.5B). [0422] In a subsequent experiment, RAJI cells, a Burkitt’s lymphoma cell line, which only express CD99 and not CD276, were treated with single antigen anti-CD19 CAR-T cells, single antigen anti-CD276 CAR-T cells, CAR-T cells expressing the AND CAR T-2 logic pair, and single antigen anti-CD99 CAR-T cells. An increase in cell death (as measured by an increase in caspase 3/7 incucyte reagent) was observed only with the single-antigen anti- Attorney Docket No.: UNCO-064/001WO 300978-2237 CD99 CAR-T cells, and not the CAR-T cells expressing the logic pair of the present disclosure. (FIG.5C). [0423] In another experiment, Applicants tested the anti-tumor efficacy of the CAR-T cells expressing logic pairs of the present disclosure against DIPG BT245 and DIPG007 xenograft models. Briefly, NSG (immunodeficient) mice were implanted with DIPG-Luc tumor cells in the pons. After tumor establishment, a single dose (20 x 10⁶ CAR-T cells) of either, single antigen anti-CD19 CAR-T cells, single antigen anti-CD99 CAR-T cells, single antigen anti- CD276 CAR-T cells, or CAR-T cells expressing the AND CAR T-2 logic pair of Example 1 (“AND CAR T-2 CAR-T cells”) was delivered systemically. Kaplan Meier survival analysis of xenografts from BT245 mouse models after each CAR-T treatment show survival of about 30 days in mice treated with single antigen anti-CD19 CAR-T cells, about 50 days in mice treated with single antigen anti-CD99 CAR-T cells, about 75 days in mice treated with single antigen anti-CD276 CAR-T cells, and over 200 days in mice treated with AND CAR T-2 CAR-T cells (FIG.6A). Similarly, Kaplan Meier survival analysis of xenografts from DPIG007 mouse models after each CAR-T treatment show survival of about 60 days in mice treated with single antigen anti-CD19 CAR-T cells, about 90 days in mice treated with single antigen anti-CD99 CAR-T cells, about 80 days in mice treated with single antigen anti- CD276 CAR-T cells, and over 100 days in mice treated with AND CAR T-2 CAR-T cells (FIG.6B). [0424] Without wishing to be bound by theory, the results presented in this example demonstrate that the logic pairs of CAR polypeptides of the present disclosure can be used to specifically target and eliminated DIPG cells, both in vitro and in vivo. [0425] Example 4. Functionality of CD99/CD276 logic gated CAR-T cells in PFA Ependymoma (PFA EPN). [0426] The following experimental example tests the functionality and specificity of CD99/CD276 logic gated CAR-T cells against posterior fossa type A (PFA) ependymoma (PFA EPN). Applicants tested the expression of CD99 and CD276 in PFA EPN patient tumors and cultured cell lines and found that CD99 and CD276 were both highly expressed in patient tumors as compared to normal cerebellum (NC), as shown by RNAseq analysis and flow cytometry in patient tumors and PFA EPN cell lines. [0427] Applicants tested the anti-tumor efficacy of CAR-T cells expressing the AND CAR T-1 logic pair and CAR-T cells expressing the AND CAR T-2 logic pair described in Example 1 against PFA EPN MAF928 cells. PFA EPN MAF928 tumor cells were treated with the CAR-T cells expressing the logic pairs at a 1:1 (tumor cell: CAR-T cell) ratio. Attorney Docket No.: UNCO-064/001WO 300978-2237 Changes in growth were measured using XCELLigence real-time measurements, which showed complete tumor lysis when the PFA EPN cells were treated with the CAR-T cells expressing the logic pairs (FIG.7). Cytokine production was also increased when PFA EPN MAF928 cells were treated with logic gated CAR-T cells at a 1:1 ratio, as compared to PFA EPN MAF928 cells treated with single antigen anti-CD19 CAR-T cells (mock) (FIG.8). [0428] Applicants also tested the anti-tumor efficacy of CD99/CD276 logic gated CAR-T cells against PFN EPN MAF928 mouse model. Briefly, NSG (immunodeficient) mice were implanted with PFN EPN MAF928-Luciferase tumor cells in the 4^th ventricle. After tumor establishment, a single dose (20 million CAR-T cells) of either, single antigen anti-CD19 CAR-T or CAR-T cells expressing the AND CAR T-2 logic pair of Example 1. BLI imaging of the tumors showed complete tumor clearance by day 7 post infusion in mice treated with the AND CAR T-2 CAR-T cells. In another experiment, MAF293 PFA EPN tumor cells expressing luciferase were implanted in the mouse’s 4^th ventricle and allowed to metastasize. After day 40 post infusion, the mice were treated with a single systemic dose of single antigen anti-CD19 CAR-T or the AND CAR T-2 CAR-T cells. BLI imaging of the tumors showed complete tumor clearance and survival of the logic gated CAR-T treated mice after 140 days. [0429] Without wishing to be bound by theory, the results described in this example demonstrate that the logic pairs of CAR polypeptides can be used to effectively target and eliminate PFA EPN cells both in viro and in vivo. [0430] Example 5. Functionality of CD99/CD276 logic gated CAR-T cells in Atypical Teratoid Rhabdoid Tumors (ATRT). [0431] The following experimental example tests the functionality and specificity of CD99/CD276 logic gated CAR-T cells against ATRT. Applicants tested the expression of CD99 and CD276 in ATRT patient tumors and found that CD99 and CD276 were both highly expressed in patient tumors as compared to normal brain cells, as shown by RNAseq analysis. [0432] Applicants tested the anti-tumor efficacy of CAR-T cells expressing the AND CAR T-2 logic pair described in Example 1 against an ATRT mouse model. Briefly, NSG (immunodeficient) mice were implanted with ATRT-Luciferase tumor cells in the 4^th ventricle. After tumor establishment, a single dose (20 million CAR-T cells) of either single antigen anti-CD19 CAR-T or CAR-T cells expressing the AND CAR T-2 logic pair was delivered systemically. BLI imaging of the tumors showed complete tumor clearance in CD99/CD276 logic gated CAR-T treated mice by day 7 post infusion. Kaplan Meier survival Attorney Docket No.: UNCO-064/001WO 300978-2237 analysis of xenografts from single antigen CD19 CAR-T treated mice showed survival of about 40 days, as compared to over 150 days for mice treated with CD99/CD276 logic gated CAR-T cells (FIG.9). [0433] Example 6. Functionality of CD99/CD276 logic gated CAR-T cells in Ewing Sarcoma. [0434] The following experimental example tests the functionality and specificity of CD99/CD276 logic gated CAR-T cells against Ewing Sarcoma. Applicants tested the expression of CD99 and CD276 in Ewing Sarcoma cell lines and found that CD99 and CD276 were both highly expressed, as shown by flow cytometry analysis. [0435] Applicants tested the anti-tumor efficacy of CD99/CD276 logic gated CAR-T cells (T cells expressing the the AND CAR T-2 logic pair described in Example 1) against orthotopic TC71 Ewing Sarcoma mouse model. Kaplan Meier survival analysis of TC71 xenografts from single antigen anti-CD19 CAR-T cell treatment, single antigen anti-CD99 CAR-T cell treatment, single antigen anti-CD276 CAR-T cell treatment, and CD99/CD276 logic gated CAR-T cell treatment showed increased survival in CD99/CD276 logic gated CAR-T cell treated mice. CAR-T cells were administered at a 20 million cell dose. Mouse death in the CD99/CD276 logic gated CAR-T cell treatment was due to an onset of graft versus host disease (GVHD) and not tumor burden (FIG.10). While there was a temporary decrease in tumor burden with both single antigen anti-CD99 CAR-T cell and single antigen anti-CD276 CAR-T cell treatments, these tumors relapsed quickly. The relapse eventually required limb amputation. Conversely, CD99/CD276 logic gated CAR-T cell treated mice experienced no relapse and therefore did not require limb amputation. [0436] Mice from each CAR-T treatment were also tested for lung metastasis by ddPCR. The presence of lung metastasis was evident with the increase in the detection of EWS-FLI1 DNA in plasma collected from single antigen anti-CD99 CAR-T cell treated mice and single antigen anti-CD276 CAR-T cell treated mice. No evidence of lung metastasis was present in mice that received CD99/CD276 logic gated CAR-T cell treatment. [0437] Without wishing to be bound by theory, the results described in this example demonstrate that the CD99/CD276 logic gated T cells of the present disclosure can be used to effectively treat Ewings Sarcoma and effectively prevent metastasis of Ewings sarcoma. [0438] Example 7. Fractionated radiation increases expression of both CD99 and CD276 in DIPG cells and Ewing Sarcoma Cells. [0439] The following experimental example tests the effect of fractionated radiation on the expression of CD99 and CD276 in DIPG and Ewing Sarcoma cells. Applicants subjected Attorney Docket No.: UNCO-064/001WO 300978-2237 DIPG BT245 cells or Ewing Sarcoma cells to fractioned low-dose radiation (4 Gy) for three consecutive days and found an increase in the expression of CD99 and CD276 after 48 hours. Without wishing to be bound by theory, these results demonstrate that the CD99/CD276 logic gated T cells of the present disclosure can be used in combination with radiation therapy to effectively treat cancer, including DIPG and Ewing sarcoma. [0440] Example 8. Heterogeneity in CD276 expression in tumor cells and functionality of CD99/CD276 logic gated CAR-T cells against CD276-low or CD276-high tumor cells. [0441] The following experimental example tests the effect of heterogeneity in CD276 expression in tumor cells. While CD99 is homogenously expressed at high levels, a significant heterogeneity in the level of CD276 expression in DIPG patient tumors is evident. [0442] Applicants tested CD99/CD276 logic gated CAR-T cells against CD276-high and CD276-low Ewing sarcoma cells. Applicants found that logic gated CAR-T cells expressing the AND CAR T-1 logic pair or the AND CAR T-2 logic pair of Example 1 were cytotoxic against both CD276-high and CD276-low expressing cells in vitro. [0443] Applicants tested CD99/CD276 logic gated CAR-T cells against low CD276 expressing K562 cells, a human erythromyeloid leukemia cell line. Stable mCherry- expressing K562 cells were co-cultured with CD99/CD276 logic gated CAR-T cells and single antigen CD276 CAR-T cells at a tumor:effector (T:E) ratio of 1:2 for 24 hours and the CAR-T cell cytotoxic efficacy was determined by measuring the presence of live mCherry- positive cells by flow cytometry. A reduction in the mCherry positive/live cells in both CD99/CD276 logic gated CAR-T cells and single antigen CD276 CAR-T cell treated lines compared to that treated with single antigen CD19 CAR-T cells (mock) was demonstrated. [0444] Applicants tested the CD99/CD276 logic gated CAR-T cells for the ability to mitigate the hurdle of tumor escape of low-CD276 expressing cells, by performing an in vivo study using subcutaneously established K562 mice xenografts. These tumor bearing mice were infused with equal number of single antigen CD19 CAR-T cells, single antigen CD276 CAR- T cells, or CD99/CD276 logic gated CAR-T cells and tumor volume was measured periodically using a caliper. The CD99/CD276 logic gated CAR-T cells performed better in eliminating tumor burden and mainly in resisting tumor relapse compared to that of single antigen CD276 CAR-T cells (FIG.11). [0445] Without wishing to be bound by theory, these results presented in this example demonstrate that the CD99/CD276 logic gated CAR-T cells of the present disclosure can be used to target and eliminate cancer cells even when they express low levels of CD276.

Claims

Attorney Docket No.: UNCO-064/001WO 300978-2237 What is claimed is: 1. A pair of chimeric antigen receptor (CAR) polypeptides comprising an anti-CD276 CAR polypeptide and an anti-CD99 CAR polypeptide, wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD276 antigen binding domain comprising an anti-CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; iii) a hinge domain comprising a CD28 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 40; iv) a transmembrane domain comprising a CD28 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 44; v) a costimulatory domain comprising a CD28 costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 48; and wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising the anti-CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation polypeptide comprising the amino acid sequence of SEQ ID NO: 52. 2. The pair of CAR polypeptides of claim 1, wherein the anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 63, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 65. 3. A pair of CAR polypeptides comprising an anti-CD276 CAR polypeptide and an anti- CD99 CAR polypeptide, wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; Attorney Docket No.: UNCO-064/001WO 300978-2237 ii) an anti-CD276 antigen binding domain comprising an anti-CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; v) a costimulatory domain comprising a 4-1BB costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 50; and wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising the anti-CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation polypeptide comprising the amino acid sequence of SEQ ID NO: 52. 4. The pair of CAR polypeptides of claim 2, wherein the anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 64, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 65. 5. A pair of chimeric antigen receptor (CAR) polypeptides comprising an anti-CD276 CAR polypeptide and an anti-CD99 CAR polypeptide, wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising an anti-CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD28 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 40; iv) a transmembrane domain comprising a CD28 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 44; Attorney Docket No.: UNCO-064/001WO 300978-2237 v) a costimulatory domain comprising a CD28 costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 48; and wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD276 antigen binding domain comprising the anti-CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation polypeptide comprising the amino acid sequence of SEQ ID NO: 52. 6. The pair of CAR polypeptides of claim 1, wherein the anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 61, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 62. 7. A pair of CAR polypeptides comprising an anti-CD276 CAR polypeptide and an anti- CD99 CAR polypeptide, wherein the anti-CD99 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD99 antigen binding domain comprising an anti-CD99 scFv comprising the amino acid sequence of SEQ ID NO: 38; iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; v) a costimulatory domain comprising a 4-1BB costimulatory polypeptide comprising the amino acid sequence of SEQ ID NO: 50; and wherein the anti-CD276 CAR polypeptide comprises, from N-terminus to C-terminus, i) a signal peptide; ii) an anti-CD276 antigen binding domain comprising the anti-CD276 scFv comprising the amino acid sequence of SEQ ID NO: 12; Attorney Docket No.: UNCO-064/001WO 300978-2237 iii) a hinge domain comprising a CD8 hinge polypeptide comprising the amino acid sequence of SEQ ID NO: 42; iv) a transmembrane domain comprising a CD8 transmembrane polypeptide comprising the amino acid sequence of SEQ ID NO: 46; and v) an activation domain comprising CD3ȗ activation polypeptide comprising the amino acid sequence of SEQ ID NO: 52. 8. The pair of CAR polypeptides of claim 2, wherein the anti-CD276 CAR comprises the amino acid sequence of SEQ ID NO: 60, and the anti-CD99 CAR comprises the amino acid sequence of SEQ ID NO: 62. 9. A nucleic acid molecule comprising: at least nucleic acid sequence encoding for the anti-CD276 CAR polypeptide of the pair of CAR polypeptides of any one of claims 1-8; and at least nucleic acid sequence encoding for the anti-CD99 CAR polypeptide of the pair of CAR polypeptides of claim 1-8. 10. The nucleic acid molecule of claim 9, wherein the at least one nucleic acid sequence encoding for the anti-CD276 CAR polypeptide and the at least one nucleic acid sequence encoding for the anti-CD99 CAR polypeptide are separated by at least one nucleic acid sequence that encodes a self-cleaving peptide, preferably wherein the self-cleaving peptide is the P2A self-cleaving peptide. 11. A vector comprising the nucleic acid molecule of claim 9 or claim 10, preferably wherein the vector is a viral vector, preferably wherein the viral vector is an AAV vector or a lentiviral vector. 12. A cell expressing the pair of CAR polypeptides of any one of claims 1-8. 13. The cell of claim 12, wherein the cell is an immune cell. 14. The cell of claim 13, wherein the immune cell is a T cell, NK cell, NK-like cell, NKT cell, or cytokine induced killer (CIK) cell, preferably wherein the immune cell is a T cell. Attorney Docket No.: UNCO-064/001WO 300978-2237 15. A population of cells of any one of claims 12-14. 16. A method of treating cancer in a subject, the method comprising administering to the subject one or more amounts of the cell population of claim 15. 17. A method of preventing cancer metastasis in a subject, the method comprising administering to the subject one or more amounts of the cell population of claim 15. 18. The method of claim 16 or claim 17, the method further comprising administering to the subject at least one additional therapy. 19. The method of claim 18, wherein the at least one additional therapy comprises at least one of radiation therapy, chemotherapy, and surgery. 20. The method of any one of claims 16-19, wherein the cancer is diffuse intrinsic pontine glioma (DIPG), acute myeloid leukemia (AML), Ewing sarcoma, posterior fossa type A (PFA) ependymoma, or an atypical teratoid rhabdoid tumor (ATRT).