EP3393511A1 - Mémoire immunitaire avantageuse provenant de vaccins pédiatriques communs pour lutter contre la maladie - Google Patents

Mémoire immunitaire avantageuse provenant de vaccins pédiatriques communs pour lutter contre la maladie

Info

Publication number
EP3393511A1
EP3393511A1 EP16880067.0A EP16880067A EP3393511A1 EP 3393511 A1 EP3393511 A1 EP 3393511A1 EP 16880067 A EP16880067 A EP 16880067A EP 3393511 A1 EP3393511 A1 EP 3393511A1
Authority
EP
European Patent Office
Prior art keywords
strain
virus
lynn
rna pol
edmonston
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP16880067.0A
Other languages
German (de)
English (en)
Inventor
Patrick H. HO
Ravi KOLLA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
La Jolla Institute for Allergy and Immunology
Original Assignee
La Jolla Institute for Allergy and Immunology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by La Jolla Institute for Allergy and Immunology filed Critical La Jolla Institute for Allergy and Immunology
Publication of EP3393511A1 publication Critical patent/EP3393511A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/125—Picornaviridae, e.g. calicivirus
    • A61K39/13—Poliovirus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
    • A61K39/165—Mumps or measles virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/20—Rubella virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/245—Herpetoviridae, e.g. herpes simplex virus
    • A61K39/25—Varicella-zoster virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
    • A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16641—Use of virus, viral particle or viral elements as a vector
    • C12N2710/16643—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16711—Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16734—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18411—Morbillivirus, e.g. Measles virus, canine distemper
    • C12N2760/18434—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18711—Rubulavirus, e.g. mumps virus, parainfluenza 2,4
    • C12N2760/18734—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/32011—Picornaviridae
    • C12N2770/32611—Poliovirus
    • C12N2770/32634—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/36011—Togaviridae
    • C12N2770/36211—Rubivirus, e.g. rubella virus
    • C12N2770/36234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to the field of disease treatment.
  • the present invention relates to the implementation of treatments for disease, from the approach of targeting pre-existing human immunity as a vehicle to specifically target and destroy target cells.
  • Vaccines provide a mechanism to promote safe development of long-lived immune memory against a pathogen(s) by avoiding deleterious effects of actual pathogen infection.
  • a number of vaccines are routinely administered to children to prevent the contraction of debilitating infectious diseases and immune memory from these vaccines can be measured decades following administration.
  • T cells including CDS and CD4 cytotoxic T cells
  • CDS and CD4 cytotoxic T cells play a key role in the defense against intracellular pathogens and tumor cells.
  • T cell immune responses are driven by the recognition of foreign peptides presented by major histocompatibility complex class I and class II (MHC I and MHC EC) molecules at the cell surface.
  • MHC I and MHC EC major histocompatibility complex class II
  • T cell epitopes is therefore important for understanding disease pathogenesis and etiology as well as for vaccine design.
  • T cells response has been implicated in providing vaccine mediated protection. However few T cell epi opes from vaccines have been identified.
  • the up regulated state translates into the body's own immune system recognizing its own cells as foreign and begins launching an attack on its own healthy cells.
  • a further problem with existing therapies is the risk associated with tissues begin to build tolerance to the administered therapy whereby mutations enable cancer cells to bypass the therapeutic agent proliferate and they not only become unresponsive to the treatment but potentially further create an environment whereby no other alternative therapies are available.
  • a cancer immunotherapy method that provides an immune response specifically targeted to cancer cells that does not target healthy cells or checkpoint inhibitor (i.e. CTLA4 or PDl) targeting therapies in which increasing evidence shows reduced utility in cancers of low mutational burden.
  • checkpoint inhibitor i.e. CTLA4 or PDl
  • the present inventors disclose a treatment that has a targeted approach towards known epitopes recognized by the immune system from previous immunity. This approach has significant implications for patient care and treatment success by promoting more rapid, non-self, and targeted cytolytic activity.
  • a method of treating cancer comprising, a) providing a subject having or suspected of having a cancer and b) administering a vector to the subject, wherein the vector directs expression of one or more peptide antigens on a target cell of the subject and wherein a memory or recall immune response is elicited against the one or more peptide antigens.
  • a method of treating cancer comprising a) providing a subject having or suspected of having a cancer; and b) administering a composition to the subject, wherein the composition comprises one or more peptide antigens, wherein a memory or recall immune response is elicited against the one or more peptide antigens.
  • the subject prior to the administering of (b), was vaccinated against a pathogen, non-limiting examples of which include a vaccination against chickenpox, measles, mumps, rubella, shingles/varicella zoster or polio.
  • a subject is vaccinated with another suitable live or attenuated pathogen, or pathogen antigen.
  • the subject prior to the administering of (b), was vaccinated with at least one of the one or more peptides selected from Tables 1 to 10, or one or more other antigens derived from a pathogen.
  • the subject may have been vaccinated 1 day, 1 month, 6 months, or 1 year to 100 years prior to administering of (b). Accordingly, in certain aspects, the administering of (b) elicits a recall immune response in the subject, wherein the recall immune response is directed against the target cell and/or at least one of the one or more peptide antigens.
  • the one or more peptide antigens bind to MHC class I or MHC class II and can recall CD8 T-cell or CD4 T-cell responses.
  • the subject is further administered an anti-cancer therapy.
  • the anticancer therapy may be administered prior to, concurrently with and/or after the administering of vector or peptides of (b).
  • One or more anti-cancer therapies can be administered alone, or in combination.
  • the anti-cancer therapy can be any suitable cancer-therapy.
  • the anti-cancer therapy comprises surgical resection.
  • the anti-cancer therapy comprises a radiation therapy, chemotherapy or an immunotherapy.
  • a radiation therapy comprises external beam radiation, proton therapy, or internal radiation therapy.
  • an immunotherapy comprises chimeric antigen receptor (CAR)-T immunotherapy.
  • CAR-T immunotherapy sometimes comprises administering CAR T- cells configured to specifically bind to and kill the target cell.
  • an immunotherapy comprises administering an antibody or antibody fragment that specifically binds to a cell-surface antigen, non-limiting examples of which include CD20, CD30, CD33, CD47 (SIRP-1 alpha soluble receptor), CD52, CD138, CD274, CD279, PD-L1 , CTLA-4, programmed cell death 1 (PD-1), CD33, EGFR, ERBB2 (CD340), ERBB3, VEGF, VEGFR, GM-2, gp-100, EPCAM, CD19, CD3, CEA, gpA33, mucins, TAG-72, CAIX, PSMA, folate-binding protein, GD2, GD3, Integrin ⁇ 3, Integrin ⁇ 5 ⁇ 1, IGF1R, EPHA3, TRAILR1 , TRAILR2, RANKL, FAP or Tenascin.
  • the antibody may be bi-specific and may bind to two cell surface antigens.
  • the immunotherapy comprises administering an antibody or T-cell that specifically binds a checkpoint blocker.
  • an immunotherapy comprises administering an antibody or antibody fragment that specifically binds to a tumor marker
  • a peptide antigen described herein is derived from a pathogen (e.g. , a peptide expressed by a pathogen).
  • the one or more peptide antigens are selected from a peptide listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • a target cell is a cell that is or has been infected with a
  • a target cell may be a cell that is or has been infected with a virus, bacteria, parasite or protozoa. In some embodiments, a target cell is not infected with a pathogen.
  • a pathogen can be a human pathogen and may be a virus, fungus, bacteria, parasite or protozoa.
  • a pathogen is a non-human pathogen, or the peptide antigen is conserved between human and another species, or wherein the peptide antigen cross-reacts between human and another species.
  • a pathogen is a virus, non-limiting examples of which include a virus of the order Flaviviridae,
  • Retroviridae Orthomyxoviridae, Arenaviridae, or Mononegavirales, or a virus of the family Togaviridae, Reoviridae, picornaviridae, herpesviridae or Bunyaviridae.
  • a target cell is a cancer cell or neoplastic cell.
  • a target cell is a metastatic cancerous cell.
  • a cancer cell, metastatic cancerous cell or neoplastic cell include cells of a carcinoma, sarcoma, neuroblastoma, cervical cancer cell, hepatocellular cancer cell, mesothelioma, glioblastoma, myeloma, lymphoma, neoplastic lymphocyte, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma,
  • a subject is a mammal. In some aspects a subject is a non-human mammal. In some aspects, a subject is a human. In some embodiments, wherein prior to the administering of a vector or peptide of (b), a subject was infected with the pathogen, thereby inducing, eliciting or promoting a recall immune response in the subject to certain pathogen antigens.
  • a subject has, or is suspected of having a cancer.
  • examples of a cancer include a neoplasia derived from lung, thyroid, head or neck, nasopharynx, throat, nose, sinus, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, mouth, esophagus, stomach, duodenum, ileum, jejunum intestine, colon, rectum, uterus, urethra, ovary, cervix, endometrium, bladder, testicle, penis, prostate, kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin.
  • a cancer examples include a carcinoma, sarcoma, neuroblastoma, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, myeloma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, cervical cancer, breast cancer, liver cancer, pancreatic cancer, brain cancer, lung cancer, skin cancer, ovarian cancer, and testicular cancer.
  • a cancer is an infection-induced cancer non-limiting examples of which include a hepatocellular carcinoma, cervical cancer, head and neck squamous cell carcinoma, adult T-cell leukemia/lymphoma, Burkitt lymphoma, Merkel cell carcinoma, kaposi sarcoma, bladder cancer and gastric cancer.
  • a hepatocellular carcinoma cervical cancer, head and neck squamous cell carcinoma, adult T-cell leukemia/lymphoma, Burkitt lymphoma, Merkel cell carcinoma, kaposi sarcoma, bladder cancer and gastric cancer.
  • a cancer comprises a low mutational burden.
  • a cancer comprising a low mutational burden include pilocytic astrocytoma, ALL, medulloblastoma, kidney chromophobe, thyroid, CLL, neuroblastoma, glioblastoma, and pancreatic cancer.
  • a method herein comprises administering a vector that selectively directs expression of one or more peptide antigens on a target cell.
  • a vector directs expression of the one or more peptide antigens on the cell surface of the target cell.
  • the one or more peptide antigens are expressed or presented on the cell surface of the target cell. Presentation of a peptide antigen on the surface of a cell may include co-expression of a peptide in the presence of TAP (transporter associated with antigen processing).
  • a vector comprises a nucleic acid encoding one or more non-self-peptide antigens (e.g. , one or more of the antigens of Tables 1 to 10.
  • a vector comprises a promoter operatively linked to a nucleic acid encoding the one or more peptides.
  • a promoter of a vector is sometimes inducible by a factor, for example a transcription factor derived from a pathogen, a mutated human protein, and/or one or more viral proteins.
  • a factor is a viral transcription factor.
  • the administering of a vector or protein of (b) comprises
  • microparticles, nanoparticles, liposomes, exosomes or recombinant virus may comprise a vector or one or more peptides.
  • the microparticles, nanoparticles, liposomes, exosomes or recombinant virus may comprise a vector or one or more peptides.
  • administering of a vector or protein of (b) comprises selectively delivering microparticles, nanoparticles, liposomes, exosomes or recombinant virus to a target cell.
  • the administering of a vector of (b) comprises administering a nucleic acid to the subject, wherein the nucleic acid comprises the vector.
  • Non-limiting examples of a vector include a plasmid, and a linear nucleic acid molecule.
  • a vector comprises a CRISPR element, and/or the vector is configured to express (CRISPR- associated protein-9 nuclease) CAS9.
  • a vector is integrated into the target cell by a method comprising CRISPR and (CRISPR-associated protein-9 nuclease) CAS9.
  • the administering comprises direct intra-tumoral injection. In some aspects, the administering comprises intravenous injection, intraperitoneal injection, subcutaneous injection or intramuscular injection.
  • the method further comprises c) initiating, eliciting, promoting, or enhancing an immune response in the subject, wherein the immune response is directed against the target cell and/or target antigen.
  • the eliciting of (c) comprises initiating, eliciting, promoting or enhancing a recall response in the subject to the one or more peptide antigens.
  • the eliciting of (c) comprises administering a vaccine to the subject.
  • a vaccine is selected from a vaccine for chickenpox, measles, mumps, rubella, and polio.
  • the eliciting of (c) comprises administering a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises at least one of the one or more of the peptide antigens.
  • the pharmaceutical composition comprises an adjuvant.
  • the eliciting of (c) comprises administering an agent that modulates an immune response in the subject.
  • the agent increases, enhances, promotes or elicits an innate immune response.
  • the agent comprises a checkpoint blocker.
  • the agent increases, enhances, promotes or elicits a recall immune response.
  • the agent comprises an antibody.
  • the antibody specifically binds to the one or more peptide antigens.
  • the agent comprises a nucleic acid, synthetic chemical, or small molecule.
  • a method herein further comprising administering a checkpoint blocker, or providing TAP to the target cell, wherein the TAP promotes peptide:MHC expression.
  • composition herein comprises an adjuvant, exosomes,
  • a composition is a pharmaceutical composition or pharmaceutical formulation comprising one or more peptides (e.g. , a peptide listed in Tables 1 to 10).
  • a composition (e.g. , a pharmaceutical composition) comprises a vector configured to direct expression of one or more peptide antigens on a target cell of a subject, wherein the one or more peptide antigens is selected from a peptide listed in Tables 1 to 10.
  • the present invention provides methods and compositions for eliciting an immune response against target cells.
  • known or predicted, antigens from vaccines or other developed immunity are engineered to serve as tags for the targeted cells so as to provide a targeted identification method for the target cells that are recognized by the subjects existing immune system, inducing the subjects immune system to attack the tagged or target cells.
  • the present invention provides a targeted treatment for patients diagnosed with cancer.
  • the present invention is a preventative treatment for subjects who have been determined to be at risk of developing particular cancer.
  • At risk patients may be determined through various methods known in the art or in the future including but not limited to genetic predispositions and hereditary traits.
  • the treatment is administered as a primary treatment or in conjunction with other treatments well known in the art.
  • the disease target cells can be administered a factor, for example but not limited to a protein or variant of a protein, which is not present in healthy cells through restricted delivery to a specific tissue.
  • the target cells have a mutation not present in healthy cells that results in expression of factor, for example but not limited to a protein or variant of a protein, which is not present in healthy cells.
  • the expression of factor that is unique to or predominantly specific to the disease cell enables expression of the antigen from the gene construct.
  • antigens are specifically expressed in target cells through administration of a gene construct encoding an antigen wherein expression or presentation of the antigen requires a factor (e.g. protein, gene, SNP, transcription factor) selectively expressed in the target cells.
  • the gene construct contains the antigen with a promoter driven only by a factor selectively expressed in the target cells (e.g. a cancer cell specific transcription factor).
  • a gene construct containing an antigen with a promoter driven by factors (e.g. proteins, peptides) expressed only in the virally transformed cells provides for specific expression of the antigen only in the target cell and therefore provides labeling of the target cells (e.g. a cancer cell) with the antigen.
  • the methods of the present invention can be used to target pre-, active and metastatic cancerous cells.
  • the expression of transformed viral genes in cancerous cells enables the selective synthesis of proteins or peptides in these cells that are necessary for expression of the antigen from the gene construct.
  • the method involves administration of a gene construct containing the antigen driven by a viral transformed promoter that requires transformed viral genes found in the cancerous cell for expression of the antigen.
  • peptide epitopes disclosed herein in cancers of low mutational burden or that are not sensitive to immune-based therapies such as but not limited to treatment with checkpoint inhibitors or CAR-T is contemplated.
  • Expression of peptide epitopes disclosed herein in combination with other immune-based therapies in such cancers represents a novel utility to make these cancers immune sensitive.
  • the antigen to be selectively expressed and presented by the target cells is an antigen from a vaccine including but not limited to childhood vaccines, e.g. chickenpox, measles, mumps, rubella, and polio.
  • the antigen to be selectively expressed and presented by the target cells is a subsequence, homologue, variant or derivative of an antigen from a vaccine.
  • the present inventors have identified peptides derived from vaccine strains of viruses used in live attenuated vaccines administered during child- and adulthood including chickenpox, measles, mumps, rubella, and polio that are broadly bound by HLA class I and class II molecules represented in humans from diverse ethnic, racial, and geographic backgrounds that can be used to recall memory T cell responses.
  • compositions that comprise one or more peptides listed in Tables 1 to 10, or a subsequence, homologue, variant or derivative thereof are directly administered to the cancer tissue of the patient.
  • the composition can be administered by for example but not limited to viral vectors, micro- or nano- particles, direct injection, lipid particles, exosomes, gene, and/or adjuvanted delivery methods.
  • a composition described herein is administered by direct tissue injection, intratumoral injection, intravenous injection, intraperitoneal injection, subcutaneous injection or intramuscular injection.
  • a subject is vaccinated prior to, concurrently with, or after the administering of (b).
  • a vaccination is a booster vaccination.
  • the booster vaccination comprises at least one peptide listed in Tables 1 to 10.
  • the booster vaccination is a booster vaccination against chickenpox, measles, mumps, rubella, or polio.
  • an anti-cancer therapy comprises administering combinations of one or more small molecules, immune checkpoint inhibitors optionally selected from IDO/TDO inhibitors, and epigenetic regulators such as HDAC inhibitors.
  • an anti-cancer therapy comprises administering, alone or in combination, one or more cancer vaccines optionally based on cancer-associated tumor antigens, or neo-antigens.
  • the one or more of the one or more peptide antigens are linked to a targeting antibody, antibody fragment or nanobody that is internalized by the target cell.
  • a pre-existing T cell memory is measured prior to the
  • the method comprises boosting immune memory in the subject by administering a vaccines or antigen that stimulates a recall immune response against the one or more peptide antigens.
  • a recall and targeting of a pre-existing immune responses leads to tumor cell killing and optionally a subsequent 'abscopal' effect with systemic, cancer-specific immune responses.
  • the one or more peptide antigens comprise full antigens or complete proteins derived from the pathogens.
  • a diagnostic tool for measuring immune response to a vaccine or recall immunity to a target cell comprising measuring an immune response to one or more peptides listed Tables 1 to 10.
  • the measurement of recall immunity is prior to administration of a peptide listed in any of Tables 1 to 10.
  • the measurement of recall immunity is prior to administration of a vector configured to expresses at least one peptide listed in any of Tables 1 to 10.
  • a subject is vaccinated prior to, concurrently with, or after the administering of a vector or peptide of (b).
  • the vaccination is a booster vaccination.
  • the booster vaccination comprises at least one peptide listed in Tables 1 to 10.
  • the booster vaccination is a booster vaccination against hickenpox, measles, mumps, rubella, or polio. DETAILED DESCRIPTION
  • An "associated symptom, disease or disorder” as used herein refers to a symptom, disease or disorder that develops in conjunction with, following or as a result of a disease state (e.g. cancer). This includes acute and chronic diseases or disorders, short and long term disease and disorders, as well as related symptoms thereof.
  • a subject is a mammal.
  • mammals include humans, non-human primates (e.g. , apes, gibbons, chimpanzees, orangutans, monkeys, macaques, and the like), domestic animals (e.g., dogs and cats), farm animals (e.g., horses, cows, goats, sheep, pigs) and experimental animals (e.g. , mouse, rat, rabbit, guinea pig).
  • a subject is a non-human mammal.
  • a subject is a rodent (e.g. , a rat or mouse).
  • a subject is a human.
  • diagnosis refers to a relative probability that a disease or condition (e.g. cancer) is present in the subject. In some instances, as will be appreciated by any one of skill in the field of medicine, a diagnosis may not be absolute or definite.
  • virus bacteria
  • oncovirus bacteria
  • cancer virus bacteria
  • tumor virus bacteria
  • tumor virus bacteria
  • fung virus fungal virus
  • tumor virus a class of triggers that are associated with the development of or are the cause of a cancer, either currently known or yet to be confirmed or discovered.
  • the cause can be related to the insertion of viral or bacterial DNA or RNA into the genome of the target cell. .
  • Vaccination regimes means vaccines, for example but not limited to MMR, oral polio vaccine, injectable polio vaccine, and chicken pox including those administered during childhood or adulthood.
  • recall response means an immune response to an antigen to which a subject has previously been exposed.
  • a recall or memory response is therefore an immune response subsequent to the initial antigen exposure and immune response.
  • a recall response may occur following exposure of the subject to the antigen for a second (secondary), third (tertiary), fourth, fifth, sixth, seventh, eighth, ninth, tenth, or any subsequent antigen exposure.
  • a recall or memory response is distinguished from a primary response to an antigen; a primary response is an immune response that occurs when a subject is exposed to an antigen for the first time. In a primary response, naive B and T cells become activated, develop higher specificity and affinity, expand, and develop memory cells. In contrast, recall immune responses are believed to be attributed to reactivation of long-lived, antigen-primed B and T lymphocytes that arise from differentiated B and T cells in a quiescent state.Thus, a "recall response" is an immune response in which antigen-primed cytotoxic T cell, Thl, Th2, and/or B cells participate.
  • target cell refers to cells, which are affected by a disease or disorder, contribute to a disease or disorder, predisposed to transform into a disease or disorder and/or are targets of treatment.
  • Target cells are distinguished from healthy or non-disease cells in that healthy or non-disease cells have normal function or are not desired targets of treatment.
  • Non-limiting examples of target cells comprise cells, tissue or derivatives thereof from cancer or any other desired targeted cells subset.
  • Target cells may include cancer cells that have been transformed by a virus or bacteria, including but not limited to a Burkitt's lymphoma cancer cell, nasopharyngeal cancer cell, Hodgkin lymphoma cancer cell and stomach cancer cell (Epstein Barr Virus), Kaposi sarcoma cancer cell (human herpes virus 8); cervical cancer cell, penis cancer cell, anus cancer cell, vagina cancer cell, vulva cancer cell, throat and mouth cancer cell (human papillomavirus); liver cancer cell (hepatitis B and C viruses), breast cancer cell or gliobastoma multiform ceil (human cytomegalovirus), T cell leukemia cell and lymphoma ceil (Human T-lymphotrophic virus 1), mesothelioma cell, brain cancer cell, bone cancer cell and lymphomas (Simian virus 40), stomach cancer cells (Helicobacter pylori and merkel cell cancer cell (Merkel cell polyoma vims).
  • a target cell is a cancer cell or neoplastic cell.
  • a target cell is a metastatic cancerous cell.
  • Non-limiting examples of a cancer cell or neoplastic cell include a carcinoma, sarcoma, neuroblastoma, cervical cancer cell, hepatocellular cancer cell, mesothelioma, glioblastoma, myeloma, lymphoma, neoplastic lymphocyte, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma or fibrosarcoma.
  • a target cell is a cell that is or has been infected with a pathogen. In certain embodiments, a target cell is a cell that is or has been infected with a virus, bacteria, parasite or protozoa.
  • a pathogen can be a mammalian pathogen.
  • a pathogen is a human pathogen.
  • a pathogen can be a virus, bacteria, parasite or protozoa.
  • Non-limiting examples of a pathogen include a virus of the order Flaviviridae, Retroviridae, Orthomyxoviridae, Arenaviridae, or Mononegavirales, a virus of the family Togaviridae, Reoviridae, picornaviridae, herpesviridae or Bunyaviridae.
  • a virus is a human papillomavirus.
  • a virus is a hepatitis B or hepatitis C virus.
  • a virus is a Merkel cell polyomavirus.
  • compositions of the invention are administered to a subject or patient as part of a treatment described herein.
  • Delivery mechanisms refer to mechanisms (chemical, biological, physical and otherwise) that are utilized to introduce a package into the patient's system and cells.
  • the present invention is not limited to the delivery mechanisms disclosed herein and one skilled in the art would appreciate that other mechanisms known in the art, as a whole, in part and in combination, can be used to deliver the packages to the target and desired cells.
  • treatment may refer to any delay in onset, reduction in the frequency or severity of symptoms, amelioration of symptoms, improvement in patient comfort or function, decrease in the occurrence of a given condition or disease or condition or disease symptoms in a patient, decrease in severity of the condition or disease state etc.
  • the effect of treatment can be compared to an individual or pool of individuals not receiving a given treatment, or to the same patient prior to, or after cessation of, treatment.
  • treatment may be complete (no detectable symptoms) or partial, such that fewer symptoms are observed than would likely occur absent treatment.
  • antigen refers to any protein, peptide, biological component,
  • epitope refers to the specific region of the antigen that elicits the immune response.
  • peptide and protein refers to polymers of amino acid residues.
  • the terms include amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer.
  • a peptide or protein described herein includes an epitope.
  • variant refers to a protein or peptide that deviates from a reference protein or peptide sequence. Modified and variant proteins or peptides may therefore have greater or less activity or function than a reference protein or peptide but at least retain partial activity or function of the reference protein or peptide.
  • nucleic acid sequences With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations.
  • each codon in a nucleic acid except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan
  • TGG which is ordinarily the only codon for tryptophan
  • amino acid sequences one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.
  • substitutions for one another 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g. , Creighton, Proteins (1984)).
  • a “label” or a “detectable moiety” is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means.
  • useful labels include 32P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins or other entities, which can be made detectable, e.g. , by incorporating a radiolabel into a peptide or antibody specifically reactive with a target peptide. Any method known in the art for conjugating an antibody to the label may be employed, e.g. , using methods described in Hermanson, Bioconjugate Techniques 1996, Academic Press, Inc., San Diego.
  • recombinant when used with reference, e.g. , to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified.
  • recombinant cells express genes that are not found within the native (non- recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all.
  • heterologous when used with reference to portions of a nucleic acid
  • nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature.
  • the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g. , a promoter from one source and a coding region from another source.
  • a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g. , a fusion protein).
  • treatment may refer to any delay in onset, reduction in the frequency or severity of symptoms, amelioration of symptoms, improvement in patient comfort or function, decrease in the occurrence of a given condition or disease or condition or disease symptoms in a patient, decrease in severity of the condition or disease state etc.
  • the effect of treatment can be compared to an individual or pool of individuals not receiving a given treatment, or to the same patient prior to, or after cessation of, treatment.
  • treatment may be complete (no detectable symptoms) or partial, such that fewer symptoms are observed than would likely occur absent treatment.
  • an "agent” as used herein refers to any molecule (e.g. antibody, nucleic acid,
  • an agent that modulates an immune response is a molecule (e.g. antibody, nucleic acid, synthetic chemical, small chemical molecule) that when administered to a subject modulates an immune response in the subject.
  • the agent modulates, inhibits, blocks, decreases, increases, enhances, promotes or elicits an acute or chronic immune response.
  • the agent modulates stimulation, activation proliferation, number or activity of immune proteins or cells (e.g. T cells, B cells, macrophages, monocytes, dendritic cells, cytokines etc.)
  • the agent modulates an innate immune response.
  • the agent modulates a recall immune response.
  • the agent modulates an immune response to one or more of the peptides listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • an agent administered to a subject to treat cancer when administered to a subject in a therapeutically effective dose or amount is an agent that binds one or more of the proteins listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the agent binds one or more of the proteins listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof. . In some embodiments, the agent binds the complex of an immune cell or immune protein bound to one or more of the proteins listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the agent modulates the activity or expression of one or more type of immune cell or protein (e.g. T cells, B cells, macrophages, monocytes, dendritic cells, cytokines) or a combination thereof.
  • the agent modulates the stimulation of T cells, activation of T cells, proliferation of T cells, number of T cells or activity of T cells, or a combination thereof.
  • the agent modulates the stimulation of B cells, activation of B cells, proliferation of B cells, number of B cells or activity of B cells, or a combination thereof.
  • the agent modulates stimulation, activation, proliferation, number or activity, or a combination thereof, of B cells generating antibodies (e.g. antibodies to one or more of the proteins listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof).
  • the agent modulates production or activity of cytokines
  • immune activators chemokines, growth factors and TNF family members (e.g. AREG, Granzyme, Histamine, IFNa/b, IFNg, IL12, IL15, IL16, IL17a-f, ILlb, 112, IL21, IL22, IL23, IL25, IL27, GM-CSF, IL33, IL4, IL5, IL6, IL7, IL8, IL9, LFA-1 , LIF,
  • lymphotoxin Mac- 1, MCP- 1, MlPla, Perforin, TGF-B, TNFa, VLA-4, CCL1 , CCL11 , CLL17, CCL1, CCL20, CCL22, CCL3, CCL4, CCL5, CXCL10, CXCL13, CXCL8, RANTES, CXCL12, G-CSF, M-CSF, VEGF, PDGF, 4-1BB, APRIL, BAFF, CD27, CD30, CD30L, CD70, DR3, DR4, DR5, FAS, FASL, GITR, HVEM, LIGHT, LTB, OX40, Ox40L, TACI, TRAIL, TWEAK, IL11, IL14 or IL10).
  • the agent modulates activity or expression of immune cells or proteins involved in an immune response to one or more of the proteins listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the immune response is an innate immune response.
  • the immune response is a recall immune response.
  • the agent modulates stimulation of T cells, activation of T cells, proliferation of T cells, number of T cells or activity of T cells, or a combination thereof, wherein the T cells are specific for one or more of the proteins listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the agent modulates stimulation of B cells, activation of B cells, proliferation of B cells, number of B cells or activity of B cells, or a combination thereof, wherein the B cells are specific for one or more of the proteins listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the method involves selectively expressing in the target cells (e.g. cancer cells, viral, bacterial, parasite or protozoa infected cells) an antigen that the subject has previously developed immunity against.
  • the method involves selectively expressing in target cells an antigen from a vaccine that the subject has previously received resulting in a recall immune response specific to the target cell.
  • the antigen is from a vaccine the subject received in childhood including but not limited to one or more of the vaccines for chickenpox, measles, mumps, rubella, and polio.
  • the expression of particular antigens that are non-self immunogenic peptides e.g.
  • non-self immunogenic peptides results in a signature labeling of the target cells with non-self immunogenic peptides.
  • the signature labeling is providing a means for the target cells to be singled out and differentiated from healthy cells that are not expressing the particular antigens.
  • the expression of non-self immunogenic peptides elicits a memory immune response against the target cells that are expressing the particular antigens.
  • memory T cells e.g. CDS and/or CD4 T cells, specific to the non-self immunogenic peptides are reactivated.
  • the treatment comprises an antigen from a vaccine that is administered to a patient who has previously developed immunity against the antigen, resulting for example from childhood vaccination regimes, where the vaccine was effective in developing immunity against the disease for which the vaccine was designed.
  • the patient has been vaccinated against a disease and has developed immunity to these infections such that immunity can be detected, boosted and measured.
  • the patient received vaccination against the disease during childhood.
  • the patient has been previously infected with a virus, bacteria, parasite or protozoa expressing the antigen and has developed immunity to the antigen due to this prior infection.
  • a subject has been previously vaccinated against a pathogen.
  • the developed immunity is against chickenpox, measles, mumps, rubella and polio.
  • the subject' s immune system is able to recall an immune response developed from a previous vaccination regime or infections.
  • the subject may be administered a booster vaccination to prime immune memory (e.g. increase antibody titers, memory T cells) prior to administration of a method or composition of the present invention.
  • immune memory e.g. increase antibody titers, memory T cells
  • immunity may be induced using other vaccination methods other than childhood vaccines.
  • the antigen is selectively expressed in the target cells through administration of a gene construct encoding an antigen wherein expression or presentation of the antigen requires a factor (e.g. protein, gene, SNP, transcription factor) selectively expressed in the target cells.
  • a factor e.g. protein, gene, SNP, transcription factor
  • the gene construct contains the antigen with a promoter driven only by a factor selectively expressed in the target cells (e.g. a cancer cell specific transcription factor).
  • this specific expression of the necessary factor in the target cells is a result of the target cells being infected by a virus, bacteria, parasite or protozoa such that there is expression of transformed viral genes or bacterial, parasitic or protozoa genes present in the target cells which encode for the necessary factors to express the antigen from the gene construct.
  • the gene construct comprises the antigen with a promoter driven only by a factor selectively expressed in the target cells (e.g. a cancer cell specific or infected cell specific transcription factor).
  • a gene construct that contains a promoter driven only by a factor expressed by target cells that have been infected with a particular virus, bacteria, protozoa or parasite is administered to the subject, is ingested by the subjects cells and the viral, bacterial, parasitic or protozoa genes in the target cells enables the selective expression of proteins or peptides in these cells that are needed for expression of the antigen from the gene construct. Only the target cells that contain the viral, bacterial, parasitic or protozoa genes will express the antigen resulting in a recall immune response specific to the target cells.
  • the antigen is specifically expressed in target cells by targeted delivery of the antigen to the target cells.
  • methods for targeted delivery of the antigen to the target cells including administration by direct intratumoral injection, micro- or nano-particles, Liposome, PEGylation lipofectamine, adenovirus, lentivirus, or other viral gene vector, and/or CRISPR/CAS9.
  • the present invention comprise administering an optimized
  • the optimized package comprising one or more antigens (e.g. , peptide antigens).
  • antigens e.g. , peptide antigens
  • peptide antigens include a peptide selected from any one of Tables 1 to 10, or a subsequence, homologue, variant or derivative of a peptide listed in any one of Tables 1 to 10.
  • the optimized package included one or more epitopes from antigen against which the subject has immune memory, e.g. epitopes from childhood vaccines.
  • the optimized package comprises one or more CD4 and/or CDS T cell epitopes, for example, one or more of the epitopes listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the optimized package contains epitopes selected for their broad recognition by HLA class I molecules of subjects from diverse ethnic and geographically backgrounds.
  • the method includes administering the antigen and epitopes in combination with factors that induce an increase of epitope presentation by MHC molecules (i.e. TAP expression) and/or activation and recruitment of APCs (i.e. GM-CSF, anti-immune suppressive agents, or chemokines).
  • TAP expression factors that induce an increase of epitope presentation by MHC molecules
  • APCs i.e. GM-CSF, anti-immune suppressive agents, or chemokines
  • the present invention provides a gene construct encoding the antigen and genes for increased expression of cytokines, immune activators, chemokines, growth factors and TNF family members to amplify the inflammatory T cell response by the recalled immune system.
  • the gene constructs comprises genes for one or more of AREG, Granzyme, Histamine, IFNa/b, IFNg, IL12, IL15, IL16, IL17a-f, ILlb, 112, IL21, IL22, IL23, IL25, IL27, GM-CSF, IL33, IL4, IL5, IL6, IL7, IL8, IL9, LFA-1, LIF, lymphotoxin, Mac-1, MCP-1, MlPla, Perforin, TGF-B, TNFa, VLA-4, CCL1, CCL11, CLL17, CCL1, CCL20, CCL22, CCL3, CCL4, CCL5, CXCL10, CXCL13, CXCL8, RANTES, CXCL12, G-CSF, M-CSF, VEGF, PDGF, 4-1BB, APRIL, BAFF, CD27, CD30, CD30L, CD70, DR3,
  • the treatment is directed towards cancer, including but not limited to cancers involving or caused by viral, parasitic or bacterial infection that can be targeted by local administration or tissue-targeting agents, or cancers of low mutational burden of reduced efficacy following other cancer imunotherapies.
  • Non-limiting examples of cancers that may be treated by the present invention include a neoplasia derived from lung, thyroid, head or neck, nasopharynx, throat, nose, sinus, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, mouth, esophagus, stomach, duodenum, ileum, jejunum intestine, colon, rectum, uterus, urethra, ovary, cervix, endometrium, bladder, testicle, penis, prostate, kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, and skin; a carcinoma, sarcoma, neuroblastoma, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, myeloma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma
  • a cancer is an infection-induced cancer.
  • infection-induced cancers include a hepatocellular carcinoma, cervical cancer (human papillomavirus), head and neck squamous cell carcinoma (HNSCC), glioblastoma, adult T-cell leukemia/lymphoma, liver cancer (hepatitis B and C viruses), Burkitt's lymphoma and Kaposi sarcoma (Epstein-Barr virus), Merkel cell cancer (e.g. , Merkel cell carcinoma)(Merkel cell polyoma virus), bladder cancer and gastric cancer.
  • cervical cancer human papillomavirus
  • HNSCC head and neck squamous cell carcinoma
  • glioblastoma glioblastoma
  • adult T-cell leukemia/lymphoma hepatitis B and C viruses
  • Burkitt's lymphoma and Kaposi sarcoma Epstein-Barr virus
  • Merkel cell cancer e.g. , Merkel cell carcinoma
  • a cancer comprises a low mutational burden, non-limiting examples of which include pilocytic astrocytoma, ALL, medulloblastoma, kidney chromophobe, thyroid, CLL, neuroblastoma, glioblastoma, and pancreatic cancer.
  • a method comprises administering a checkpoint blocker. In certain embodiments, a method comprises adoptive transfer of T-cells containing a chimeric antigen receptor (CAR).
  • CAR chimeric antigen receptor
  • the present invention provides epitopes from childhood vaccines that can be administered in the methods described herein.
  • compositions comprising proteins and peptides comprising epitopes from childhood vaccines, including but not limited to chickenpox, measles, mumps, rubella, and polio.
  • the protein or peptide comprises, consists or consists essentially of one or more of the amino acid sequences listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the present invention provides a composition comprising combinations of epitopes from childhood vaccines.
  • the present invention provides combinations of one or more proteins or peptides each comprising, consisting or consisting essentially of a different amino acid sequence listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the present invention provides a composition comprising a gene construct encoding one or more epitopes from childhood vaccines.
  • the present invention provides a gene construct encoding one or more of the amino acid sequences listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • a composition comprise a viral construct configured to express one or more of the amino acid sequences listed in any one of Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • a composition comprises agents to improve peptide:HLA expression (e.g., TAP).
  • a composition comprises agents to improve immune infiltration.
  • a composition comprises agents to reduce checkpoint inhibition.
  • a composition comprises T-cells that are adoptively transferred containing CAR specific to one or more of the peptides listed in Tables 1 to 10.
  • epitopes are selected for their
  • HLA class I or class II molecules broad recognition by HLA class I or class II molecules of subjects from diverse ethnic, racial and geographically backgrounds.
  • the present invention provides a uniquely optimized
  • the composition of the present invention comprises viral, bacterial, parasitic, protozoa or cancer specific transformed promoter, epitopes, proteins, factors that increase epitope expression in MHC pockets and genes that increase cytokine expression.
  • one or more epitopes are selected from the peptides in Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.
  • the composition comprises CD4 and/or CD8 T cell
  • the composition comprises T cell (e.g. CDS and/or CD4 T cells) epitopes from the measles vaccine, comprising one or more or a combination of the peptides listed in any one of Tables 1 or 6.
  • the composition comprises CD4 and/or CD8 T cell epitopes from the rubella vaccine, comprising one or more or a combination of the peptides listed in Tables 4 or Table 9.
  • the composition comprises CD4 and/or CD8 T cell epitopes from the polio vaccine, comprising one or more or a combination of the peptides listed in Tables 3 and 8.
  • the composition comprises CD4 and/or CD8 T cell epitopes from the chicken pox/varicella vaccine, comprising one or more or a combination of the peptides listed in Tables 5 (5a and 5b) or 10.
  • the composition comprises proteins, peptides or epitopes from two or more different vaccines (e.g. measles, mumps, rubella, polio or chicken pox vaccine).
  • the composition comprises proteins, peptides or epitopes from two or more, three or more, four or more, or five different vaccines.
  • the composition may contain the same number of proteins, peptides or epitopes from each of the two or more vaccines or may contain a different number of proteins, peptides or epitopes from each of the two or more vaccines.
  • each T cell epitope binds only a subset of naturally occurring HLA Class II
  • HLA class II molecules in the human population and this repertoire of HLA class II molecules varies from one person to another and from one ethnic population to another, in certain embodiments of the presentation invention, it is desirable to select a mix of several peptides covering different HLA class II molecules to generate an immune response in a broad segment of the population. Further, in other embodiments of the present invention, it is desirable to select peptides that elicit an immune response (e.g. T cell response or an immune response (e.g. T cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.
  • an immune response e.g. T cell response or an immune response (e.g. T cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.
  • an epitope or combination of epitopes that have a HLA class II repertoire covering a high fraction of a worldwide population, and which also produce an immune response (e.g. T cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.
  • an immune response e.g. T cell response
  • each T cell epitope binds only a subset of naturally occurring HLA Class I
  • HLA class I molecules in the human population and this repertoire of HLA class I molecules varies from one person to another and from one ethnic population to another, in certain embodiments of the presentation invention, it is desirable to select a mix of several peptides covering different HLA class I molecules to generate an immune response in a broad segment of the population. Further, in other embodiments of the present invention, it is desirable to select peptides that elicit an immune response (e.g. T cell response or an immune response (e.g. T cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.
  • an immune response e.g. T cell response or an immune response (e.g. T cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.
  • an epitope or combination of epitopes that have a HLA class I repertoire covering a high fraction of a worldwide population, and which also produce an immune response (e.g. T cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.
  • an immune response e.g. T cell response
  • the methods or compositions of the present invention it is desirable for the methods or compositions of the present invention to include as few peptides as possible, but at the same time to be able to treat the majority of patients in a worldwide population with the same method or composition.
  • Such a method or should contain a combination of peptides capable of binding to a HLA Class II repertoire covering a high fraction of a worldwide population, and the resulting peptide-HLA complexes should be recognized as epitopes (e.g. T cell epitopes) in the subject so as to induce an immune response.
  • the composition of the present invention further comprises cytokines, immune activators, chemokines, growth factors or TNF family members or a gene for increased expression of cytokines, immune activators, chemokines, growth factors or TNF family members to amplify the inflammatory T cell response by the recalled immune system.
  • the composition comprises one or more of or genes for one or more of AREG, Granzyme, Histamine, IFNa/ ⁇ , IFNgamma, IL12, IL15, IL16, IL17a-f, ILlb, 112, IL21 , IL22, IL23, IL25, IL27, GM-CSF, IL33, IL4, IL5, IL6, IL7, IL8, IL9, LFA- 1, LIF, lymphotoxin, Mac- 1, MCP-1 , MlPla, Perforin, TGF- ⁇ , TNFa, VLA-4, CCL1 , CCL11, CLL17, CCL1 , CCL20, CCL22, CCL3, CCL4, CCL5, CXCL10, CXCL13, CXCL8, RANTES, CXCL12, G-CSF, M-CSF, VEGF, PDGF, 4- IBB, APRIL, BAFF, CD27, CD30
  • compositions are delivered to the target disease cells via one or more delivery systems depending on the indication, disease state, severity, clinical utility and other relevant parameters that may impact the desired efficacy of delivery and expression of the T cell epitopes and/or antigens.
  • the delivery system is engineered to deliver the package to a specific cell subset of interest.
  • the composition is delivered to the target cell and other cells of interest using delivery methods comprising one or more but at least one of the methods from the group comprising: Adenovirus (AdV); Adeno-associated virus (AAV); Lenti virus; Vaccinia virus; Oncolytic viruses; Respective disease causing live, attenuated, or inactivated virus; Micro/nano particles; Adjuvant emulsified;
  • AdV Adenovirus
  • AAV Adeno-associated virus
  • Lenti virus Lenti virus
  • Vaccinia virus Oncolytic viruses
  • Respective disease causing live, attenuated, or inactivated virus Micro/nano particles
  • Adjuvant emulsified Adjuvant emulsified
  • the one or more delivery methods can be used in combination, alone, and in combinations in part thereof. Parts of particular delivery methods may be combined to other delivery methods to form new delivery methods. Other delivery methods well known in the art can be utilized to deliver the composition to the target cells.
  • one or more epitopes are selected from the peptides listed in Tables 1 to 10, or a subsequence, homologue, variant or derivative thereof, are delivered to the target cell using the delivery methods disclosed herein.
  • a peptide's immunogenicity more particularly one or more epitopes from the peptides listed in Tables 1 to 10, or a subsequence, homologue, variant or derivative thereof, may be modified.
  • the modifications to the peptides and/or antigens administered comprise one or more of the modifications from the group comprising: Oxidization; Reduction; Citrullination; Glycatation (including but not limited to: prenylation, myristylation, palmitolation); Nitration; Di-sulfide bonding (Cysteine); Transglutamination; Deamidation; Misfolding; Single amino acid substitutions; Genetic frameshift mutations.
  • the modifications are not intended to be limiting by scope or category but rather an illustration of how the peptides may be constructed in the delivery mechanisms.
  • compositions for use according to the methods of the invention described herein can be chosen by the individual physician in view of the patient's condition. See e.g. , Fingl et al. 1975, in "The Pharmacological Basis of Therapeutics," Ch. 1 p. 1 ; which is incorporated herein by reference in its entirety. Any suitable route of administration can be used for
  • routes of administration include topical or local (e.g. , transdermally or cutaneously, (e.g. , on the skin or epidermis), in or on the eye, intranasally, transmucosally, in the ear, inside the ear (e.g. , behind the ear drum)), enteral (e.g. , delivered through the gastrointestinal tract, e.g. , orally (e.g. , as a tablet, capsule, granule, liquid, emulsification, lozenge, or combination thereof), sublingual, by gastric feeding tube, rectally, and the like), by parenteral administration (e.g.
  • parenterally e.g. , intravenously, intra-arterially, intramuscularly, intraperitoneally, intradermally, subcutaneously, intracavity, intracranially, intraarticular, into a joint space, intracardiac (into the heart), intracavernous injection, intralesional (into a skin lesion), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intrauterine, intravaginal, intratumoral, intravesical infusion, intravitreal), the like or combinations thereof.
  • a composition herein is provided to a subject.
  • a composition that is provided to a subject is often provided to a subject for self- administration or for administration to a subject by another (e.g. , a non-medical professional).
  • a composition described herein can be provided as an instruction written by a medical practitioner that authorizes a patient to be provided a composition or treatment described herein (e.g. , a prescription).
  • a composition can be provided to a subject wherein the subject self-administers a composition orally, intravenously or by way of an inhaler, for example.
  • compositions herein can be formulated to be compatible with a particular route of administration or use.
  • Compositions for parenteral, intradermal, or subcutaneous administration can include a sterile diluent, such as water, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents.
  • the preparation may contain one or more preservatives to prevent microorganism growth (e.g.
  • compositions herein is substantially free of a chelator (e.g. , a zinc chelator, e.g. , EDTA or EGTA).
  • a chelator e.g. , a zinc chelator, e.g. , EDTA or EGTA.
  • Compositions for injection include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion.
  • suitable carriers include physiological saline, bacteriostatic water, Cremophor ELTM (BASF, Parsippany, NJ) or phosphate buffered saline (PBS).
  • the carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g. , glycerol, propylene glycol, and polyethylene glycol), and suitable mixtures thereof. Fluidity can be maintained, for example, by the use of a coating such as lecithin, or by the use of surfactants.
  • Antibacterial and antifungal agents include, for example, parabens, chlorobutanol, phenol, ascorbic acid and thimerosal.
  • Polysorbate 20 and polysorbate 80 can be added into the formulation mixture, for example, up to 1%.
  • Other non- limiting additives include histidine HC1, ⁇ , ⁇ -trehalose dehydrate.
  • compositions for use according to the methods of the invention in a local rather than systemic manner, for example, via direct application to the skin, mucous membrane or region of interest for treating, including using a depot or sustained release formulation.
  • active ingredients can be administered alone.
  • active ingredients can be administered in combination with one or more additional materials, for example, as two separate compositions or as a single composition where the additional material(s) is (are) mixed or formulated together with an active ingredient.
  • an active ingredient can be formulated with additional excipients, or additional active ingredients.
  • the active ingredients when administered in the forms described herein can attain concentrations at a target tissue such as the nose, mucous membranes, the bronchi, the skin, etc. that cannot be attained by the usual intravascular administration of the active ingredients.
  • compositions can be manufactured by any suitable manner, including, e.g. , by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tableting processes.
  • compositions for use in accordance with the invention thus can be formulated in any suitable manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active compounds into preparations which can be used pharmaceutically.
  • Proper formulation can depend upon the route of administration chosen.
  • any suitable formulation, ingredient, excipient, the like or combinations thereof as listed in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, 18th edition, 1990. can be used with a composition described herein.
  • the various materials listed herein, alone or in combination can be incorporated into or used with the materials described in Remington's.
  • Any suitable techniques, carriers, and excipients can be used, including those understood in the art; e.g. , in Remington's Pharmaceutical Sciences, above.
  • the pages in the attached Appendix from Remington's Pharmaceutical Sciences are incorporated herein by reference in their entirety, including without limitation for all of the types of formulations, methods of making, etc.
  • the composition may be formulated, for example, as a topical formulation.
  • the topical formulation may include, for example, a formulation such as a gel formulation, a cream formulation, a lotion formulation, a paste formulation, an ointment formulation, an oil formulation, and a foam formulation.
  • the composition further may include, for example, an absorption emollient.
  • At least part of the affected area of the mammal is contacted with the composition on a daily basis, on an as-needed basis, or on a regular interval such as twice daily, three times daily, every other day, etc.
  • the composition can be administered for a period of time ranging from a single as needed administration to administration for 1 day to multiple years, or any value there between, (e.g. , 1 -90 days, 1 - 60 days, 1 - 30 days, etc.).
  • the dosages described herein can be daily dosages or the dosage of an individual administration, for example, even if multiple administrations occur (e.g. , 2 sprays into a nostril).
  • compositions described herein relate to methods of treating or preventing cancer through administration of compositions described herein to the upper respiratory track/bronchi in a mammal in need thereof, for example, by contacting at least part of the upper respiratory tract/bronchi of a mammal with a therapeutically effective amount of a composition as described above or elsewhere herein.
  • the composition can be, for example, formulated as an aerosol formulation, including formulated for use in a nebulizer or an inhaler.
  • the composition further may include other pharmaceutically acceptable components such as a preservative.
  • compositions that include, for example, a composition as described herein and an aerosolized pharmaceutically acceptable carrier solution or dry powder.
  • the compositions may be formulated, for example, to be substantially absorbed by a bronchus.
  • the compositions also may include, for example, one or more of dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, and the like.
  • the compositions can be formulated for use in a nebulizer or an inhaler, for example.
  • carrier defines a chemical compound that facilitates the incorporation of a compound into cells or tissues.
  • DMSO dimethyl sulfoxide
  • a pharmaceutical carrier for a composition described herein can be selected from castor oil, ethylene glycol, monobutyl ether, diethylene glycol monoethyl ether, corn oil, dimethyl sulfoxide, ethylene glycol, isopropanol, soybean oil, glycerin, zinc oxide, titanium dioxide, glycerin, butylene glycol, cetyl alcohol, and sodium hyaluronate.
  • a pharmaceutical carrier for certain of such hydrophobic compounds can be a co-solvent system comprising benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase.
  • a common co-solvent system used is the VPD co-solvent system, which is a solution of 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant POLYSORBATE 80TM , and 65% w/v polyethylene glycol 300, made up to volume in absolute ethanol.
  • co-solvent system can be varied considerably without destroying its solubility and toxicity characteristics.
  • identity of the co-solvent components can be varied: for example, other low-toxicity nonpolar surfactants can be used instead of POLYSORBATE 80TM; the fraction size of polyethylene glycol can be varied; other biocompatible polymers can replace polyethylene glycol, e.g. , polyvinyl pyrrolidone; and other sugars or polysaccharides can substitute for dextrose.
  • hydrophobic pharmaceutical compounds can be employed, if required.
  • Liposomes and emulsions are well known examples of delivery vehicles or carriers for hydrophobic drugs and drug compositions.
  • Certain organic solvents such as dimethylsulfoxide also can be employed, although usually at the cost of greater toxicity.
  • the compounds can be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent.
  • the pharmaceutical compositions described herein can be administered to a patient per se, or in pharmaceutical compositions where they are mixed with other active ingredients, as in combination therapy, or suitable carriers or excipient(s).
  • the compounds and compositions can be formulated with salts or excipients, such as for example, sodium or meglumine.
  • salts or excipients such as for example, sodium or meglumine.
  • compositions described herein can preferably be stable over an extended period of time, for example on the order of months or years.
  • Compositions described herein in some embodiments, comprise a preservative.
  • the preservative can comprise a quaternary ammonium compound, such as benzalkonium chloride, benzoxonium chloride, benzethonium chloride, cetrimide, sepazonium chloride, cetylpyridinium chloride, or domiphen bromide (BRADOSOL®).
  • the preservative can comprise an alkyl-mercury salt of thiosalicylic acid, such as thiomersal, phenylmercuric nitrate, phenylmercuric acetate or phenylmercuric borate.
  • the preservative can comprise a parabens, such as methylparaben or propylparaben.
  • the preservative can comprise an alcohol, such as chlorobutanol, benzyl alcohol or phenyl ethyl alcohol.
  • the preservative can comprise a biguanide derivative, such as chlorohexidine or polyhexamethylene biguanide.
  • the preservative can comprise sodium perborate, imidazolidinyl urea, and/or sorbic acid.
  • the preservative can comprise stabilized oxychloro complexes, such as known and commercially available under the trade name PURITE®).
  • the preservative can comprise polyglycol-polyamine condensation resins, such as known and commercially available under the trade name POLY QUART® from Henkel KGaA.
  • the preservative can comprise stabilized hydrogen peroxide generated from a source of hydrogen peroxide for providing an effective trace amount of resultant hydrogen peroxide, such as sodium perborate tetrahydrate.
  • the preservative can be benzalkonium chloride.
  • the preservative can enable a composition to be used on multiple occasions.
  • the preservative can reduce the effects of one or more of acid exposure, base exposure, air exposure, heat, and light on the active ingredient.
  • the compounds and compositions used herein can include any suitable buffers, such as for example, sodium citrate buffer and/or sequestering agents, such as edetate disodium sequestering agent.
  • Ingredients such as meglumine, may be added to adjust the pH of a composition or compound described herein.
  • Compounds and compositions described herein may comprise sodium and/or iodine, such as organically bound iodine.
  • Compositions and compounds used herein may be provided in a container in which the air is replaced by another substance, such as nitrogen.
  • compositions suitable for use in the technology which include compositions where the active ingredients are contained in an amount effective to achieve its intended purpose.
  • a "therapeutically effective amount” means an amount to prevent, treat, reduce the severity of, delay the onset of or inhibit a symptom of a cancer.
  • the symptom can be a symptom already occurring or expected to occur. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.
  • a therapeutically effective amount can describe the amount necessary for a significant quantity of the composition to contact the desired region or tissue where prevention or treatment of a cancer is desired.
  • compositions described herein can be administered at a suitable dose, e.g. , at a suitable volume and concentration depending on the route of administration.
  • dosages of an administered composition, vector, factor, agent or peptide can be from 0.001 - 200 grams, or 0.001 - 50 grams, 0.001 - 10 grams, etc.
  • the amount can be, for example, from 0.001 - 0.1 grams, 0.1 - 5 grams, 5 - 10 grams, 10 - 15 grams, 15 - 20 grams, 20 - 25 grams, 25 - 30 grams, 30 - 35 grams, 35 - 40 grains, 40 - 45 grams, 45 - 50 grams and 50 - 200 grams.
  • a composition, vector, factor, agent or peptide can be provided in a concentration, for example, of 1 mg/kg to 5000 mg/kg, 50 mg/kg to 1000 mg/kg, 50 mg/kg to 500 mg/kg, 150 mg/kg to 350 mg/kg or 350 mg/kg to 1000 mg/kg.
  • composition, vector, factor, agent or peptide described herein can be administered at a concentration of at least 50 mg/kg, at least 100 mg/kg, at least 150 mg/kg, at least 200 mg/kg, at least 150 mg/kg, at least 200 mg/kg, at least 250 mg/kg, at least 300 mg/kg, at least 350 mg/kg, at least 400 mg/kg, at least 450 mg/kg, or at least 500 mg/kg.
  • a composition, vector, factor, agent or peptide described herein can be administered at a concentration of about 100 mg/kg, about 150 mg/kg, about 200 mg/kg, about 150 mg/kg, about 200 mg/kg, about 250 mg/kg, about 300 mg/kg, about 350 mg/kg, about 400 mg/kg, about 450 mg/kg, or about 500 mg/kg.
  • Volumes suitable for intravenous administration are well known. For example, 50 ml - 100 ml of a composition, vector, factor, agent or peptide at a working concentration of between about 200 mg/kg to about 350 mg/kg can be safely administered intravenously to an adult human subject.
  • the amount delivered can be any suitable amount, for example, in order to contact the desired tissue in a therapeutically effective manner.
  • the compositions can be delivered to the nose, and the amount delivered to each nostril can be from about 20 microliters to about 1500 microliters, 50 microliters to about 1000 microliters, or 50 microliters to about 500 microliters.
  • composition described herein can be delivered to the nose in a volume of about 50, 100, 200, 300, 400 or 500 microliters for example.
  • compositions can, if desired, be presented in a pack or dispenser device, which can contain one or more unit dosage forms containing the active ingredient.
  • the pack can for example comprise metal or plastic foil, such as a blister pack.
  • the pack or dispenser device can be accompanied by instructions for administration.
  • the pack or dispenser can also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, can be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert.
  • Compositions comprising a compound of the invention formulated in a compatible pharmaceutical carrier can also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.
  • kits can include one or more of the compositions, vectors, factors, agents or peptides described herein, formulations of the same, combination drugs and products and other materials described herein.
  • the products, compositions, kits, formulations, etc. can come in an amount, package, product format with enough medication to treat a patient for 1 day to 1 year, 1 day to 180 days, 1 day to 120 days, 1 day to 90 days, 1 day to 60 days, 1 day to 30 days, or any day or number of days there between.
  • kits including a composition, vector, factor, agent or peptide of the invention, combination compositions and pharmaceutical formulations thereof, packaged into suitable packaging material.
  • a kit optionally includes a label or packaging insert including a description of the components or instructions for use in vitro, in vivo, or ex vivo, of the components therein.
  • Exemplary instructions include instructions for a method, treatment protocol or therapeutic regimen.
  • a kit can contain a collection of such components, e.g. , two or more conjugates alone, or in combination with another therapeutically useful composition (e.g. , an anti-proliferative or immune-enhancing drug).
  • the term "packaging material” refers to a physical structure housing the components of the kit.
  • the packaging material can maintain the components sterilely, and can be made of material commonly used for such purposes (e.g. , paper, corrugated fiber, glass, plastic, foil, ampules, vials, tubes, etc.).
  • Kits can include labels or inserts.
  • Labels or inserts include "printed matter," e.g. , paper or cardboard, or separate or affixed to a component, a kit or packing material (e.g. , a box), or attached to an ampule, tube or vial containing a kit component.
  • Labels or inserts can additionally include a computer readable medium, optical disk such as CD- or DVD-ROM/RAM, DVD, MP3, magnetic tape, or an electrical storage media such as RAM and ROM or hybrids of these such as magnetic/optical storage media, FLASH media or memory type cards.
  • Labels or inserts can include identifying information of one or more components therein, dose amounts, clinical pharmacology of the active ingredient(s) including mechanism of action, pharmacokinetics (PK) and pharmacodynamics (PD). Labels or inserts can include information identifying manufacturer information, lot numbers, manufacturer location and date. [00129] Labels or inserts can include information on a condition, disorder, disease or symptom for which a kit component may be used. Labels or inserts can include instructions for the clinician or for a subject for using one or more of the kit components in a method, treatment protocol or therapeutic regimen. Instructions can include dosage amounts, frequency or duration, and instructions for practicing any of the methods, treatment protocols or therapeutic regimes set forth herein. Kits of the invention therefore can additionally include labels or instructions for practicing any of the methods and uses of the invention described herein.
  • Labels or inserts can include information on any benefit that a component may provide, such as a prophylactic or therapeutic benefit. Labels or inserts can include information on potential adverse side effects, such as warnings to the subject or clinician regarding situations where it would not be appropriate to use a particular composition. Adverse side effects could also occur when the subject has, will be or is currently taking one or more other medications that may be incompatible with the composition, or the subject has, will be or is currently undergoing another treatment protocol or therapeutic regimen which would be incompatible with the composition and, therefore, instructions could include information regarding such incompatibilities.
  • Kits can additionally include other components. Each component of the kit can be enclosed within an individual container and all of the various containers can be within a single package. Invention kits can be designed for cold storage.
  • Effective immunity against a pathogen entails (i) the development of highly specific, neutralizing, and non-self reactive antibodies and T cells and (ii) results in the development of immune memory cells that patrol the body and provides lifelong protection.
  • Immune memory cells are uniquely positioned to rapidly and robustly expand and neutralize a specific pathogen if repeat exposure occurs.
  • Vaccines provide a mechanism to promote safe development of long-lived immune memory against a pathogen(s) by avoiding the deleterious effects of actual pathogen infection. The inventor approach activates and redirects the long-lived immune memory derived from vaccines to fight cancer.
  • the present invention can be used in combination with other cancer and cancer-immune-based therapies to increase efficacy of patient treatment.
  • Peptide epitopes disclosed herein can be delivered in combination with viral vectors including oncolytic viruses like T-Vec (Imlygic).
  • T-Vec is the first oncolytic virus approved in the US and has been shown of utility in the treatment of patients with recurrent melanoma.
  • Peptide epitopes disclosed herein can be cloned into the herpes simplex virus type 1 (HSV1) virus for expression in tumor tissue to combine oncolytic potential with increased tumor immunogenicity.
  • HSV1 herpes simplex virus type 1
  • AdV adenovirus
  • AdAV adeno- associated virus
  • vaccinia virus are in advanced clinical development. These viruses have potential for selective tumor mediated killing through direct tumor injection or engineered tumor specificity.
  • CTLA-4 (Ipilumimab) and PDl(Nivolumab / Keytruda) are two presently approved targets of antibody-based checkpoint inhibitors. These antibodies non- specifically block inhibitory receptors on T cells that maintain T cells in an activated state.
  • Recent publications from Alexanderov et al (Accessed online, December 21, 2016 at ⁇ URL:http://www.nature.corn/nature/journal/v500/n7463/full/naturel2477.htrnl>) and others highlight the efficacy of these therapies may be tied to the mutational burden of the specific tumor and in tumors with low mutational burden, checkpoint inhibitors may be of limited utility.
  • Peptide epitopes disclosed herein can be delivered to the tumor will increase the immunogenicity of by bringing immune memory derived from childhood vaccines to more robustly kill cancerous and pre-cancerous tissue.
  • Non-limiting examples of peptide epitopes are listed in Tables 1 to 10.
  • Chimeric Antigen receptor T cell therapies are presently in advanced clinical trials for various cancers. These therapies entail the isolation of patient T cells and re- engineering of T cell specificity to the target of choosing. While these therapies have shown therapeutic promise in single-cell type tumors such as B cell lymphomas, solid tumors that are under immune- suppression and lack a single marker for targeting are presently intractable. The introduction of peptide epitopes and simultaneous engineering of T cells with specificity for the delivered epitopes would enable robust and targeted killing of epitope expressing cells.
  • cytokine and TNF-super family based therapies are in advanced clinical development for the treatment of cancer. Specifically, tumor specific expression of cytokines like IL12 and TNF superfamily members such as OX40 reduce tumor immune suppression and promote inflammation.
  • oncolytic virus therapies are in development in which IL12 and OX40 are expressed by the therapeutic virus. Combination of peptide epitopes in these scenarios would increase T cell infiltration and activation in the tumor tissue.
  • Rituximab represents a particularly successful candidate in the treatment of B cell based tumors such as non-Hodgkin' s lymphoma.
  • Therapeutic antibodies recognize surface antigens of the tumor tissue and induce immune responses through phagocytosis, complement deposition, and cell cytotoxicity.
  • Combined delivery of vaccine-derived epitopes with mAbs may increase the immune potential of the tumor leading to increased killing of tumor tissue by the immune system.
  • cancer-specific mutations to enable generation or expansion of tumor-specific immunity within a patient.
  • patient cancer specific mutations are identified by a variety of sequencing methods and mutation gene products are identified and assessed for the ability to be bound by HLA molecules or the existence of mutation-specific T cells within the donor. Vaccination of these peptides/antigens in combination with adjuvant and checkpoint blockers are then used to expand mutation specific T cells.
  • various tumors have lower mutational burden and therefore cancer vaccine approaches are of limited practical utility.
  • Combination of administration of patient mutation specific peptides with childhood vaccine epitopes can be considered to improve the therapeutic potential against the tumor.
  • This approach generally entails the fusion of two antibodies or generation of bi-specific antibodies that function to bring T cells in closer proximity to malignant tissue.
  • the approach has shown early clinical potential by combined target of CD 19 and T cell markers such as CD3 to bring T cells in proximity to the cellular target and promote T cell mediated killing. Delivery of vaccine-derived T cell epitopes to target tissue and co-administration of BiTE to promote T cell infiltration into the target tissue will improve the frequency or concentration of T cells with potential to specifically kill the tumor tissue.
  • HLA A A*01:01, A*26:01, A*32:01, A*02:01, A*02:03, A*02:06, A*68:02, A*2301, A*24:02, A*03:01, A*ll:01, A*30:01, A*31:01, A*33:01, and A*68:01
  • 11 HLA B alleles B*40:01, B*44:02, B*44:03, B*57:01, B*58:01, B*15:01 B*07:02, B*35:01, B*51:01, B*53:01, and B*08:01
  • Binding predictions were performed using the consensus prediction tool available on the IEDB web site (Accessed online at ⁇ URL:http:/www.iedb.org/>). For each allele and length combination, peptides from each included vaccine strain were selected if they were in the top 1% of binders. Redundant sequences across various vaccine strains were removed and non-redundant sequences are listed in the Tables as indicated. [00144] We predicted the binding affinity of 15-mer peptides derived from childhood vaccines using the panel of 27 HLA class II DRB 1, 3/4/5, DQA1/DQB 1, and DPB1 molecules that provide broad ethnic and geographic population coverage using a consensus prediction approach. Peptides with predicted binding scores in the top 20% for a given allele were considered potential binders. Peptides predicted to bind 13 or more HLA molecules at this threshold were considered promiscuous binders. In likeness to the class I predictions, redundant sequences across various vaccine strains were removed and non-redundant sequences are listed in the Tables as indicated.
  • viral genes can become incorporated into the host genome. This viral transformation event can lead to uncontrolled proliferation and the development of various diseases and disorders including cancer. Viral, parasitic and bacterial transformation or infection of healthy cells has been identified as a common underlying cause of a great number of human cancers.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Molecular Biology (AREA)
  • Pulmonology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Communicable Diseases (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne de nouvelles méthodes de traitement du cancer, lesdites méthodes entraînant l'expression d'épitopes peptidiques sur un cancer. Les épitopes peptidiques sont sélectionnés pour déclencher une réponse immunitaire de rappel chez un sujet (par exemple, une réponse immunitaire préexistante qui peut avoir été provoquée par une vaccination), ladite réponse immunitaire étant dirigée vers le cancer. Selon certains modes de réalisation, les méthodes selon la présente invention sont utilisées en combinaison avec des thérapies existantes contre le cancer.
EP16880067.0A 2015-12-21 2016-12-21 Mémoire immunitaire avantageuse provenant de vaccins pédiatriques communs pour lutter contre la maladie Withdrawn EP3393511A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562270148P 2015-12-21 2015-12-21
US201662320488P 2016-04-09 2016-04-09
PCT/US2016/068147 WO2017112830A1 (fr) 2015-12-21 2016-12-21 Mémoire immunitaire avantageuse provenant de vaccins pédiatriques communs pour lutter contre la maladie

Publications (1)

Publication Number Publication Date
EP3393511A1 true EP3393511A1 (fr) 2018-10-31

Family

ID=59091209

Family Applications (1)

Application Number Title Priority Date Filing Date
EP16880067.0A Withdrawn EP3393511A1 (fr) 2015-12-21 2016-12-21 Mémoire immunitaire avantageuse provenant de vaccins pédiatriques communs pour lutter contre la maladie

Country Status (2)

Country Link
EP (1) EP3393511A1 (fr)
WO (1) WO2017112830A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110845583A (zh) * 2019-11-18 2020-02-28 维塔恩(广州)医药有限公司 水痘带状疱疹病毒相关抗原短肽及其应用

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10722537B2 (en) 2015-11-06 2020-07-28 Regents Of The University Of Minnesota Activation of resident memory T cells for cancer immunotherapy
CN110430894A (zh) 2017-02-01 2019-11-08 莫得纳特斯公司 编码活化致癌基因突变肽的免疫调节治疗性mrna组合物
SG11201912480SA (en) 2017-06-23 2020-01-30 Pathovax Llc Chimeric virus-like particles and uses thereof as antigen-specific redirectors of immune responses
CA3071583A1 (fr) * 2017-08-03 2019-02-07 Regents Of The University Of Minnesota Activation de lymphocytes t residents memoires pour le traitement du cancer
US20190241660A1 (en) * 2017-12-05 2019-08-08 Intendet Services, Llc Immune-stimulating peptides and checkpoint inhibitors, and uses thereof for treating cancer
EP3539562A1 (fr) * 2018-03-12 2019-09-18 Eberhard Karls Universität Tübingen Medizinische Fakultät Peptides immunothérapeutiques
KR20210110321A (ko) 2018-12-27 2021-09-07 버이뮨 아이엔씨. 접합된 바이러스-유사 입자 및 항-종양 면역 재유도제로서의 이의 용도
CN111254157A (zh) * 2019-06-06 2020-06-09 南京艾德免疫治疗研究院有限公司 靶向人源化cd30的嵌合抗原受体及其用途
US11858964B2 (en) 2020-10-19 2024-01-02 Verimmune Inc. Virus-inspired compositions and methods of redirecting preexisting immune responses using the same for treatment of cancer
EP4298443A1 (fr) * 2021-02-26 2024-01-03 The Regents Of The University Of Michigan Biocapteurs fluorescents et procédés d'utilisation de ces biocapteurs dans la détection d'événements de signalisation cellulaire

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2766205B1 (fr) * 1997-07-16 2002-08-30 Inst Nat Sante Rech Med Nouveau procede de sensibilisation de cellules presentatrices d'antigene et nouveaux moyens pour la mise en oeuvre du procede
US20040234539A1 (en) * 1999-11-03 2004-11-25 Powderject Research Limited Nucleic acid vaccine compositions having a mammalian cd80/cd86 gene promoter driving antigen expression
WO2005005465A2 (fr) * 2003-07-08 2005-01-20 Board Of Regents, University Of Texas System Procedes et compositions permettant d'ameliorer des reactions immunitaires par l'intermediaire d'antigenes de rappel
GB201106357D0 (en) * 2011-04-14 2011-06-01 Pessi Antonello Composition and uses thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110845583A (zh) * 2019-11-18 2020-02-28 维塔恩(广州)医药有限公司 水痘带状疱疹病毒相关抗原短肽及其应用

Also Published As

Publication number Publication date
WO2017112830A1 (fr) 2017-06-29

Similar Documents

Publication Publication Date Title
EP3393511A1 (fr) Mémoire immunitaire avantageuse provenant de vaccins pédiatriques communs pour lutter contre la maladie
WO2017177204A1 (fr) Influencer la mémoire immunitaire issue de vaccins pédiatriques communs pour lutter contre des maladies
Sun et al. Amplifying STING activation by cyclic dinucleotide–manganese particles for local and systemic cancer metalloimmunotherapy
Xun et al. Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma
RU2376371C2 (ru) Модифицированные рекомбинантные вакцинирующие вирусы и другие микроорганизмы и их применение
CN108883187A (zh) 用于癌症治疗的smc联合疗法
Chuang et al. Treatment with imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination
Panagioti et al. Immunostimulatory bacterial antigen–armed oncolytic measles virotherapy significantly increases the potency of anti-PD1 checkpoint therapy
Baghban Rahimi et al. Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells
AU2022201142A1 (en) Vaccine compositions and methods for restoring NKG2D pathway function against cancers
Esquerré et al. GTL001, a bivalent therapeutic vaccine against human papillomavirus 16 and 18, induces antigen-specific CD8+ T cell responses leading to tumor regression
CN116710564A (zh) 溶瘤病毒增强t细胞对有效til治疗的应答
Zhen et al. CRISPR/Cas9‐HPV‐liposome enhances antitumor immunity and treatment of HPV infection‐associated cervical cancer
US20240158802A1 (en) Mrna treatment nanoparticles
Zhang et al. Recombinant cell-penetrating trichosanthin synergizes anti-PD-1 therapy in colorectal tumor
CA3028168C (fr) Compositions et procedes d'activation de cellules presentatrices d'antigene avec un poliovirus chimerique
CN113795269A (zh) 血管活性肠肽(vip)拮抗剂的组合物和用途
US20240180890A1 (en) Vaccine adjuvant
US20240115675A1 (en) Method of treating a tumor with a combination of an il-7 protein and a nucleotide vaccine
US20220313724A1 (en) Compositions for intratumoral administration and related methods
US20230321230A1 (en) Compositions and Methods for Adjuvanted Vaccines
US20240108720A1 (en) Sole use of polymersome associated adjuvant for stimulating an immune response
Wang et al. The Role and Development of Peptide Vaccines in Cervical Cancer Treatment
CN116507721A (zh) 构建溶瘤病毒的方法
Lamb et al. ATIM-22. PHASE I TRIAL OF DRUG RESISTANT IMMUNOTHERAPY: A FIRST-IN-CLASS COMBINATION OF MGMT-MODIFIEDγδ T CELLS AND TEMOZOLOMIDE CHEMOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20180719

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20190702