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1. AU2018338647 - Novel platforms for co-stimulation, novel car designs and other enhancements for adoptive cellular therapy

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WHAT IS CLAIMED IS:
1. An immune cell or immune cell population thereof expressing (i) at least one non naturally occurring immune receptor and (ii) at least one non-naturally occurring agent that selectively activates the NF-KB signaling pathway.
2.            The immune cell or immune cell population thereof of claim 1, where the at least one non-naturally occurring immune receptor comprises at least one antigen-binding domain and at least one transmembrane domain.
3.           The immune cell or immune cell population thereof of claim 1, where the at least one non-naturally occurring immune receptor is capable of recruiting at least one TCR associated signaling module.
4.           The immune cell or immune cell population thereof of claim 1, where the at least one non-naturally occurring immune receptor is a chimeric antigen receptor (CAR) or a recombinant TCR.
5.           The immune cell or immune cell population thereof of claim 2, wherein the at least one antigen-binding domain of the at least one non-naturally occurring immune receptor binds to an antigen selected from a group consisting of CD5; CD19; CD123; CD22; CD30; CD171; CS1 (also referred to as CD2 subset 1, CRACC, MPL, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-i (CLL-1 or CLECLI); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2 8)aNeu5Ac(2-3)bDGalp(-4 )bDGlcp(1-l)Cer); TNF receptor family member B cell maturation (BCMA); Tn antigen ((Tn Ag) or (GaNAc-Ser/Thr)); prostate-specific membrane antigen (PSMA); Receptor tyrosine kinase-like orphan receptor 1 (RORI); Fins Like Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38;
CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-llRa); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha (FRa or FRI); Folate receptor beta (FRb); Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAX);
Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gpl00); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l 4)bDGlcp(1-I)Cer); transglutaminase 5 (TGS5); high molecular weight-melanoma associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEMI/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRC5D); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WTI); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-la); Melanoma associated antigen 1 (MAGE-Al); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGEl); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-i (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p5 3 ); p53 mutant; prostein; survivin; telomerase; prostate carcinoma tumor antigen-i (PCT A-i or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P450 lB 1 (CYPlB 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator ofimprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY TESl); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation Endproducts (RAGE-1); renal ubiquitous 1 (RUl); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRl); Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); and immunoglobulin lambda-like polypeptide 1 (IGLLl), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBRI, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen); Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL1lRa, IL13Ra2, CD179b-IGLll, TCRgamma-delta, NKG2D, CD32 (FCGR2A), Tn ag, Timi /HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Gonadotropin Hormone receptor (CGHR or GR), CCR4, GD3, SLAMF6, SLAMF4, HIVi envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, KSHV K8.1, KSHV-gH, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), auto antibody to desmoglein 3 (Dsg3), auto antibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IgE, CD99, Ras G12V, Tissue Factor 1 (TF1), AFP, GPRC5D, Claudin18.2 (CLD18A2 or CLDN18A.2), P-glycoprotein, STEAPi, Livl,Nectin-4,Cripto, gpA33, BST1/CD157, low conductance chloride channel, and an antigen recognized by TNT antibody.
6.           The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-dB pathway is selected from the group consisting of vFLIP K13, K13-opt, a NEMO mutant, a NEMO-fusion protein, IKK1-S176E-S180E, IKK2-S177E-S181E, RIP, IKKa, IKKO, Tcl-1, MyD88-L265, any NF-KB activating protein or protein fragment, any inhibitor of an inhibitor of NF-KB pathway, any gene editing system capable of selectively activating NF-KB, any homolog or variant thereof and any combination thereof
7.           The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-iB pathway is of non viral origin.
8.           The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-KB pathway is a gene editing system.
9.           The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-B pathway induces oligomerization of NEMO/IKKy.
10. The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-B pathway induces activation of the IKK complex.
11. The immune cell or immune cell population thereof of claim 1, wherein at least one the non-naturally occurring agent capable of selectively activating NF-KB pathway does not activate the AKT pathway.
12. The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-B pathway is expressed in a constitutive or inducible manner.
13. The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-B pathway is expressed transiently.
14. The immune cell or immune cell population thereof of claim 1, wherein the at least one non-naturally occurring agent capable of selectively activating NF-B pathway is expressed stably.
15. The immune cell or immune cell population thereof of claim 1, wherein the activity of the at least one non-naturally occurring agent capable of selectively activating NF-KB pathway is controlled post-translationally through contacting the cell with a compound.
16. The immune cell or immune cell population thereof of claim 1, where the at least one non-naturally occurring agent capable of selectively activating NF-B pathway is expressed as a fusion construct with one or more copies of a switch domain.
17. The immune cell or immune cell population thereof of claim 9, wherein the activity of the at least one non-naturally occurring agent capable of selectively activating NF-KB pathway is controlled at the post-translational level by administration of therapeutically effective amount of a compound that induces dimerization of the switch domain.
18. The immune cell or immune cell population thereof of claim 16 or 17, where the switch domain comprises one or more copies of a FKBP12 domain.
19. The immune cell or immune cell population thereof of claim 15, wherein the compound is AP20187 or Rimiducid or a homolog thereof
20.         The immune cell or immune cell population thereof of claim 1, wherein the immune cell is a T-lymphocyte (T-cell), a CAR-T cell, a TCR-expressing T cell, a tumor infiltrating lymphocyte (TIL), a tissue resident lymphocyte, a stem cell, an induced pluripotent stem cell or a Natural Killer (NK) cell.
21.         The immune cell or immune cell population thereof of claim 1, wherein the immune cell has been engineered to lack a functional native T-Cell Receptor (TCR) signaling complex and/or 2 microglobulin.
22.         The immune cell or immune cell population thereof of claim 1 and 21, wherein the at least one non-naturally occurring immune receptor and/or the at least one agent capable of selectively activating NF-B signaling pathway are cloned into an endogenous TCR gene such that the expression of the at least one non-naturally occurring immune receptor and/or the at least one agent capable of selectively activating NF-KB signaling pathway are under control of the endogenous regulatory elements/promoter for the TCR gene.
23.         The immune cell or immune cell population thereof of claim 1 that is used for the prevention and treatment of a disease selected from the group of a cancer, infectious disease, immune disease, and allergic disease.
24.         The immune cell or immune cell population thereof of claim 1, where at least one polynucleotide encodes the at least one non-naturally occurring immune receptor and the at least one non-naturally occurring agent capable of selectively activating NF-KB signaling pathway are expressed from a single promoter.
25.         The immune cell or immune cell population thereof of claim 1, where at least one polynucleotide encoding the at least one non-naturally occurring immune receptor and the at least one non-naturally occurring agent capable of selectively activating NF-KB signaling pathway are expressed using two or more separate promoters.
26.         The immune cell or immune cell population thereof of claim 24 or 25, wherein the at least one polynucleotide comprises a first nucleic acid coding sequence encoding the at least one non-naturally occurring immune receptor separated from a second nucleic acid sequence encoding the non-naturally occurring agent capable of selectively activating NF-KB such that upon expression of the first and second nucleic acid coding sequences that non-naturally occurring immune receptor and non-naturally occurring agent capable of selectively activating NF-KB are not physically or chemically linked.
27.         The immune cell or immune cell population thereof of claim 24 or 25, wherein the at least one non-naturally occurring immune receptor and/or the at least one non-naturally occurring agent capable of selectively activating NF-dB coding polynucleotide(s) are cloned into an endogenous TCR gene such that the at least one non-naturally occurring immune receptor and/or at least one non-naturally occurring agent capable of selectively activating NF-KB are under control of the endogenous regulatory elements/promoter for the TCR gene.
28.         The immune cell or immune cell population thereof of claims 21 or 27, wherein one or more constant chains of the TCR genes are functionally re-expressed.
29.         At least one recombinant polynucleotide encoding at least one non-naturally occurring immune receptor, the at least one recombinant polynucleotide comprising:
(a) a first nucleic acid domain encoding a partial or entire transmembrane and/or cytoplasmic domain and optionally the extracellular domain of an endogenous protein, wherein the endogenous protein is expressed on the surface of lymphocytes and triggers the activation and/or proliferation of the lymphocyte;
(b) optionally a polynucleotide a linker;
(c) a second nucleic acid domain operably linked to the first nucleic acid domain, wherein the second nucleic acid domain encodes one or more non-natural TCR antigen binding domain(s);
(d) an optional third nucleic acid domain encoding a costimulatory domain; and (e) an optional additional nucleic acid domain encoding an accessory module.
30.         At least one recombinant polynucleotide comprising:
a) a first nucleic acid encoding a non-naturally occurring immune receptor; and
b) a second nucleic acid encoding an accessory module comprising a selective NF-KB activator.
31.  The at least one recombinant polynucleotide of claim 30, wherein the first nucleic acid and the second nucleic acid are separated by an oligonucleotide linker encoding a cleavable peptide linker.
32.  The at least one recombinant polynucleotide of claim 30, comprising two recombinant polynucleotide such that the first nucleic acid and second nucleic acid are are expressed from separate vectors.
33.         The at least one recombinant polynucleotide of claim 30, wherein the selective NF-KB activator is a non-naturally occurring selective NF-KB activator.
34.         The at least one polynucleotide of claim 30, where the non-naturally occurring immune receptor is selected from the group consisting of a CAR, an Ab-TCR, a TFP, a cTCR, a SIR and a recombinant TCR.
35.         The at least one polynucleotide of claim 30, wherein the non-naturally occurring immune receptor comprises an (i) an extracellular antigen specific domain, (ii) a transmembrane domain, and (iii) an optional intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM), wherein (iii) is located at the C terminus of the non-naturally occurring immune receptor.
36.         The at least one polynucleotide of claim 30, wherein upon expression of the first and second nucleic acids sequences the non-naturally occurring immune receptor and selective NF-KB activator polypeptide are not physically or chemically linked.
37.         The at least one polynucleotide of claim 35, wherein the extracellular antigen-specific domain binds to any one or more of CD5; CD19; CD123; CD22; CD30; CD171; CS1 (also referred to as CD2 subset 1, CRACC, MPL, SLAMF7, CD319, and 19A24); C-type lectin like molecule-i (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l 4 )bDGlcp(l-l)Cer); TNF receptor family member B cell maturation (BCMA); Tn antigen ((Tn Ag) or (GaNAcu-Ser/Thr)); prostate-specific membrane antigen (PSMA); Receptor tyrosine kinase-like orphan receptor 1 (RORI); Fins Like Tyrosine Kinase 3 (FLT3); Tumor associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-llRa); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha (FRa or FRI); Folate receptor beta (FRb); Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); AFP/MHC complex; epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAX); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gplOO); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(- 4)bDGlcp(l 1)Cer); transglutaminase 5 (TGS5); high molecular weight-melanoma associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRC5D); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCRI); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WTI); WT1/MHC I complex; Cancer/testis antigen 1 (NY-ESO-1); NY-ESO-1/MHC I complex, Cancer/testis antigen 2 (LAGE-la); Melanoma-associated antigen 1 (MAGE-Al); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGEl); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-i (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p5 3 mutant; prostein; survivin; telomerase; prostate carcinoma tumor antigen-i (PCT A-i or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P450 IB 1 (CYPlB 1); CCCTC Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY-TESl); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation Endproducts (RAGE-1); renal ubiquitous 1 (RUl); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); HPV E6/MHC I complex; human papilloma virus E7 (HPV E7); HPV E7/MHC I complex; AFP/MHC I complex; Ras/MHC I complex; intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIR); Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); and immunoglobulin lambda-like polypeptide 1 (IGLLl), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBRi, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen); Fucosyl-GMI, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, ILI1Ra, IL13Ra2, CD179b-IGLll, TCRgamma-delta, NKG2D, CD32 (FCGR2A), Tn ag, Tim1-/HVCR1, CSF2RA (GM-CSFR alpha), TGFbetaR2, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Gonadotropin Hormone receptor (CGHR or GR), CCR4, GD3, SLAMF6, SLAMF4, HIVi envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, KSHV K8.1, KSHV-gH, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), auto antibody to desmoglein 3 (Dsg3), auto antibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA DR, HLA-G, IgE, CD99, Ras G12V, Tissue Factor 1 (TF1), AFP, GPRC5D, Claudin18.2 (CLD18A2orCLDN18A.2),P-glycoprotein,STEAPi,Livl,Nectin-4,Cripto, gpA33, BST1/CD157, low conductance chloride channel, and an antigen recognized by TNT antibody.
38.         The at least one polynucleotide of claim 30, wherein the selective NF-dB activator is selected from the group consisting of vFLIP K13, a NEMO mutant, a NEMO-fusion protein, IKK1-Si76E-S180E, IKK2-S177E-S181E, RIP, FKBPx2-RIP-ID, IKK1, FKBPx2-IKKa, IKK2, FKBPx2-IKK2, Tcl-1, MyD88-L265, any NF-KB activating protein or protein fragment, any inhibitor of an inhibitor of NF-KB pathway, a gene editing system capable of selectively activating NF-iB, an RNA interference system that selectively activating NF-KB and any combination thereof
39.   The at least one polynucleotide of claim 37, where the selective NF-KB activator is expressed as a fusion construct with one or more copies of FKBP domain.
40.         The polynucleotide of claim 35, wherein the extracellular antigen specific domain is selected from the group consisting of:
- the variable region of the heavy chain (vH) of an antibody or a fragment thereof specific for a predefined target antigen;
- the variable region of the light chain (vL) of an antibody or a fragment thereof specific for a predefined target antigen;
- a single chain variable fragment (scFv) or a fragment thereof specific for a predefined target antigens;
- an antibody fragment (e.g., Fv, a Fab, a (Fab')2) specific for a predefined target antigen;
- a single domain antibody (SDAB) fragments specific for a predefined target antigen; - a camelid vHH domain specific for a predefined target antigen;
- a non-immunoglobulin antigen binding scaffolds specific for a predefined target antigen;
- a receptors specific or a fragment thereof for a predefined target antigen;
- a ligands or a fragment thereof specific for a predefined target antigen;
- a bispecific-antibody, -antibody fragment, -scFV, -vHH, -SDAB, -non immunoglobulin antigen binding scaffold, -receptor or -ligand specific for one or more predefined target antigens; and
- an autoantigen or a fragment thereof
41.         At least one vector comprising the at least one polynucleotide of any one of claims 30-40.
42.         The at least one vector of claim 41, wherein the vector is selected from the group consisting of a DNA vector, an RNA vector, a plasmid, a lentivirus vector, adenoviral vector, AAV vector, a retrovirus vector, a baculovirus vector, a sleeping beauty transposon vector, and a piggybac transposon vector.
43.         An immune effector cell or stem cell comprising at least one recombinant polynucleotide of any of claims 30-40.
44.         An immune effector cell or stem cell comprising that at least one vector of claim 41.
45.         An immune effector cell or stem cell comprising the at least one vector of claim 42.
46.         An antigen presenting cell comprising at least one vector of claim 41.
47.         The immune effector cell or stem cell of any one of claims 43-45, wherein the immune effector cell is a human T cell, a human NKT cell or a synthetic T cell, NK cell, or a stem cell that can give rise to an immune effector cell, optionally, wherein the T cell is diaglycerol kinase (DGK) and/or Ikaros deficient and/or Brd4 deficient.
48.         A method to (i) extend the life span of an immune cell expressing, (ii) stimulate proliferation of an immune cell, (iii) stimulate cytokine production by an immune cell, (iv) enhance antigen presentation by an immune cell, (v) protect an immune cell from apoptosis, the method comprising transfecting or transforming the immune cells with a polynucleotide encoding a selective NF-B activator or a NF-B specific stimulatory polypeptide.
49.         The method of clam 48, wherein the selective NF-KB activator or a NF-KB specific stimulatory polypeptide is selected from the group consisting of vFLIP K13, K13-opt, a NEMO mutant, a NEMO-fusion protein, IKK1-S176E-S180E, IKK2-S177E-S181E, RIP, IKKt, IKK, Tcl-1, MyD88-L265, any NF-KB activating protein or protein fragment, any inhibitor of an inhibitor of NF-KB pathway, any homolog or variant thereof and any combination thereof
50.         The method of claim 49, wherein the selective NF-KB activator or a NF-KB specific stimulatory polypeptide is expressed in a constitutive or inducible manner.
51.         The method of claim 50, wherein the selective NF-KB activator or a NF-KB specific stimulatory polypeptides controlled post-translationally through contacting the T cell with a compound.
52.         The method of claim 50, where the selective NF-KB activator or a NF-KB specific stimulatory polypeptide is expressed as a fusion construct with one or more copies of FKBP domain.
53.         The method of claim 52, wherein the activity of the selective NF-B activator or a NF-KB specific stimulatory polypeptide is controlled at the post-translational level by administration of therapeutically effective amount of a compound that induces dimerization of the FKBP domain.
54.         The method of claim 51, wherein the compound is AP20187 or rimiducid.
55.         A method of making a non-naturally occurring immune receptor-expressing immune effector cell, comprising introducing at least one vector of claim 41 or at least one recombinant polynucleotide of claim 29 into an immune effector cell or a hematopoietic stem cell or progenitor cell that can give rise to an immune effector cell, under conditions such that a non-naturally occurring immune receptor is expressed and the immune effector cell comprises (i) extended life span, (ii) improved T cell proliferation, and/or (iii) reduced apoptosis compared to a CAR-T cell lacking an NFkB specific stimulatory polypeptide.
56.         The method of claim 55, further comprising:
a) providing a population of immune effector cells; and
b) removing T regulatory cells from the population, thereby providing a population of T regulatory-depleted cells;
wherein steps a) and b) are performed prior to introducing the vector or recombinant polynucleotide encoding the CAR and/or NFkB specific stimulatory polypeptide to the population.
57.         The method of claim 56, wherein the T regulatory cells are removed from the cell population using an anti-CD25 antibody, or an anti-GITR antibody.
58.         The method of claim 55, further comprising:
a)  providing   a  population   of  immune   effector   cells;   and 
b) enriching P-glycoprotein (P-gp or Pgp; MDR1, ABCB1, CD243)-positive cells from the population, thereby providing a population of P-glycoprotein (P-gp or Pgp; MDR1, ABCB1, CD243)-enriched cells;
wherein steps a) and b) are performed prior to or after introducing the vector or recombinant polynucleotide encoding the CAR and/or NFkB specific stimulatory polypeptide.
59.         The method of claim 58, wherein the P-glycoprotein positive cells are enriched using any one or more of the methods selected from the group consisting of
i) immunoselection using one or a cocktail of P-glycoprotein specific antibodies, ii) staining with one or more of fluorescent dyes that are substrates of P-glycoprotein, tetramethylrhodamine methyl ester (TMRM), Adriamycin and actinomycin-D) under conditions at which P-glycoprotein is active as a pump and enriching for cells that stain less with the dye,
iii) selection of cells that are resistant to phototoxic compounds that are substrates of P-glycoprotein, such as any one or more of TH9402, 2-(4,5-dibromo-6-amino-3-imino-3H xanthen-9-yl)-benzoic acid methyl ester hydrochloride, 2-(4,5-dibromo-6-amino-3-imino-3H xanthen-9-yl)-benzoic acid ethyl ester hydrochloride, 2-(4,5-dibromo-6-amino-3-imino-3H xanthen-9-yl)-benzoic acid octyl ester hydrochloride, 2-(4,5-dibromo-6-amino-3-imino-3H xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride, 2-(6-ethyl amino-3-ethyl imino-3H xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride, or derivatives thereof or combinations thereof, and
iv) selection of cells that are resistant to cytotoxic compounds that are substrates of P glycoprotein, such as vincristine, vinblastine, taxol, paclitaxel, mitoxantrone, etoposide, adriamycin, daunorubicin and actinomycin-D.
60.         A method of generating a population of RNA-engineered cells comprising introducing in vitro transcribed RNA or RNAs or synthetic RNA or RNAs into a cell or population of cells, where the RNA or RNAs comprises a recombinant polynucleotide or polynucleotides of claim 30.
61.         A method of providing anti-disease immunity in a subject comprising administering to the subject an effective amount of the immune effector cell or a stem cell that can give rise to an immune effector cell of any one of claims 43-47, wherein the cell is an autologous T cell or an allogeneic T cell, or an autologous NKT cell or an allogeneic NKT cell or an autologous or an allogeneic hematopoietic stem cell or an autologous or an allogeneic iPSC that can give rise to an immune effector cell.
62.         The method of claim 61, wherein the allogeneic T cell or allogeneic NKT cell or hematopoietic stem cell or iPSC lacks expression or has low expression of a functional TCR or a functional HLA.
63.         A composition comprising an immune effector cell or a stem cell that can generate immune effector cells comprising a non-naturally occurring immune receptor and a selective NFkB activator, wherein the non-naturally occurring immune receptor comprises an antigen binding domains that bind to a disease-associated antigen associated said disease-associated antigen is selected from a group consisting of. CD5, CD19; CD123; CD22; CD30; CD171; CS-i (also referred to as CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-i (CLL- Ior CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2 3)bDGalp(-4)bDGlcp(-l)Cer); TNF receptor family member B cell maturation (BCMA); Tn antigen ((Tn Ag) or (GaNAcu-Ser/Thr)); prostate-specific membrane antigen (PSMA);
Receptor tyrosine kinase-like orphan receptor 1 (RORi); FmsLike Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-I3Ra2 or CD213A2); Mesothelin; Interleukin II receptor alpha (IL-llRa); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha; Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUCI); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor I receptor (IGF-I receptor), carbonic anhydrase IX (CAX);
Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gplOO); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); Fucosyl GMl; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDGlcp(1-1)Cer); transglutaminase 5 (TGS5); high molecular weight-melanomaassociated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRC5D); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCRI); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR5IE2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE la); Melanoma-associated antigen 1 (MAGE-Al); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGEl); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-i (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p5 3 ); p53 mutant; prostein; surviving; telomerase; prostate carcinoma tumor antigen-i (PCT A-i or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P450 IB 1 (CYPlB 1 ); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator ofimprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY-TESl); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation End products (RAGE-1); renal ubiquitous 1 (RUl); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRl); Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); and immunoglobulin lambda-like polypeptide 1 (IGLLl), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBRI, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen) Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL1lRa, ILI3Ra2, CD179b-IGLlI, ALK TCRgamma-delta, NKG2D, CD32 (FCGR2A), CSPG4 HMW-MAA, Timi-/HVCRI, CSF2RA (GM-CSFR-alpha), TGFbetaR2, VEGFR2/KDR, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Chorionic Gonadotropin Hormone receptor (CGHR), CCR4, SLAMF6, SLAMF4, HIVi envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, influenza A hemagglutinin (HA), GAD, PDLI, Guanylyl cyclase C (GCC), KSHV-K8.1 protein, KSHV-gH protein, auto-antibody to desmoglein 3 (Dsg3), autoantibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA DR, HLA-G, IGE, CD99, RAS G12V, Tissue Factor 1 (TFI), AFP, GPRC5D, claudini8.2 (CLD18A2 OR CLDN18A.2)), P-glycoprotein, STEAPi, LIVi, NECTIN-4, CRIPTO, GPA33, BST1/CD157, low conductance chloride channel, and antigen recognized by TNT antibody.
64.         A method of treating or preventing a disease associated with expression of a disease associated antigen in a subject, comprising administering to the subject an effective amount of an immune effector cell comprising a non-naturally occurring immune receptor and a selective NFkB activator, wherein the non-naturally occurring immune receptor comprises an antigen binding domains that bind to a disease-associated antigen associated said disease associated antigen is selected from a group consisting of. CD5, CD19; CD123; CD22; CD30; CD171; CS-i (also referred to as CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C type lectin-like molecule-i (CLL- Ior CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2 3)bDGalp(l-4)bDGlcp(-l)Cer); TNF receptor family member B cell maturation (BCMA); Tn antigen ((Tn Ag) or (GaNAcu-Ser/Thr)); prostate-specific membrane antigen (PSMA); Receptor tyrosine kinase-like orphan receptor 1 (RORI); FmsLike Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-llRa); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha; Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAX);
Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gpl00); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); Fucosyl GMl; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDGlcp(1-1)Cer); transglutaminase 5 (TGS5); high molecular weight-melanomaassociated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRC5D); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WTI); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE la); Melanoma-associated antigen 1 (MAGE-Al); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGEl); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-i (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; surviving; telomerase; prostate carcinoma tumor antigen-i (PCT A-i or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P450 lB 1 (CYPlB 1 ); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator ofimprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY-TESl); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation End products (RAGE-1); renal ubiquitous 1 (RUl); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRl); Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); and immunoglobulin lambda-like polypeptide I (IGLLl), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP TROP2, GFRalpha4, CDH17, CDH6, NYBRi, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen) Fucosyl-GMi, PTK7, gpNMB, CDHi-CD324, DLL3, CD276/B7H3, ILI1Ra, ILI3Ra2, CD179b-IGLli, ALK TCRgamma-delta, NKG2D, CD32 (FCGR2A), CSPG4 HMW-MAA, Timi-/HVCRi, CSF2RA (GM-CSFR-alpha), TGFbetaR2, VEGFR2/KDR, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Chorionic Gonadotropin Hormone receptor (CGHR), CCR4, SLAMF6, SLAMF4, HIVi envelope glycoprotein, HTLVI-Tax, CMV pp65, EBV-EBNA3c, influenza A hemagglutinin (HA), GAD, PDLi, Guanylyl cyclase C (GCC), KSHV-K8.1 protein, KSHV-gH protein, auto-antibody to desmoglein 3 (Dsg3), autoantibody to desmoglein I (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA DR, HLA-G, IGE, CD99, RAS G12V, Tissue Factor 1 (TF), AFP, GPRC5D, claudin18.2 (CLD18A2 OR CLDN18A.2)), P-glycoprotein, STEAP1, LIV1, NECTIN-4, CRIPTO, GPA33, BST1/CD157, low conductance chloride channel, and antigen recognized by TNT antibody,
thereby treating the subject or preventing a disease in the subject.
65.         The use or method of claim 63 or 64, wherein the disease associated with expression of the disease associated antigen is selected from the group consisting of a proliferative disease, a precancerous condition, a cancer, and a non-cancer related indication associated with expression of the disease-associated antigen.
66.  The use or method of claim 65, wherein the cancer is a hematologic cancer chosen from one or more of chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma, primary effusion lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, or pre leukemia.
67.         The use or method of claim 65, wherein the cancer is selected from the group consisting of colon cancer, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine, cancer of the esophagus, melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, non-Hodgkin's lymphoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, solid tumors of childhood, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, Merkel cell cancer, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers, combinations of said cancers, and metastatic lesions of said cancers.
68.  The use or method of claim 65, wherein the disease is associated with infection by a virus including but not limited to HIVI, HIV2, HTLV1, Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus, adeno-associated virus, BK virus, Human Herpesvirus 6, Human Herpesvirus 8 influenza virus, parainfluenza virus, avian flu virus, MERS and SARS coronaviruses, Crimean Congo Hemorrhagic fever virus, rhino virus, enterovirus, Dengue virus, West Nile virus, Ebola virus, Marburg virus, Lassa fever virus, zika virus, RSV, measles virus, mumps virus, rhino virus, varicella virus, herpes simplex virus 1 and 2, varicella zoster virus, HIV-1, HTLV1, Hepatitis virus, enterovirus, hepatitis B virus, Hepatitis C virus, Nipah and Rift valley fever viruses, Japanese encephalitis virus, Merkel cell polyomavirus, or is associated with infection with mycobacterium tuberculosis, atypical mycobacteria species, Pneumocystis jirovecii, toxoplasmosis, rickettsia, nocardia, aspergillus, mucor, or candida.
69.  The use or method of claim 65, wherein the disease is an immune or degenerative disease including but not limited to diabetes mellitus, multiple sclerosis, rheumatoid arthritis, pemphigus vulgaris, ankylosing spondylitis, Hoshimoto's thyroiditis, SLE, sarcoidosis, scleroderma, mixed connective tissue disease, graft versus host disease or Alzheimer's disease.