Basic Immunology. Lecture 26 th. Immunity against tumors
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1 Basic Immunology Lecture 26 th Immunity against tumors
2 Neoplastic transformations are genetic alterations. Expression of cell surface antigens both self and non-self - seen by immune system. Ehrlich positive mechanism eliminating transformed cells. L.Thomas, McFarlane immune surveillance - recognition and destruction of non-self tumor cells on their appearance. Tumor occurrence: immune surveillance is imperfect.
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7 Tumor antigens tumor specific antigens (TSA) (no general tumor specific antigen exists) tumor specific transplantation antigens (TSTA) (mutated self antigens expressed on MHC-I) tumor associated antigens (TAA) (AFP, CEA, hcgβ, PSA, CA, LDH, β2 microglobulin) tumor associated transplantation antigens (TATA) (tumor associated antigens expressed on MHC-I)
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10 AFP Alpha (a)-fetoprotein AIM-2 Interferon-inducible protein absent in melanoma 2 ALL Acute lymphoblastic leukemia AML Acute myeloid leukemia 707-AP 707 alanine proline APL Acute promyelocytic leukemia ART-4 Adenocarcinoma antigen recognized byt cells 4 BAGE B antigen bcr-abl Breakpoint cluster region- Abelson CAMEL CTL-recognized antigen on melanoma CAP-1 Carcinoembryonic antigen peptide-1 CASP-8 Caspase 8 CDC27 Cell division cycle 27 CDK4 Cyclin-dependent kinase 4 CEA Carcinoembryonic antigen CLCA2 Calcium-activated chloride channel 2 CML Chronic myelogenous leukemia CT Cancer-testis (antigen) CTL Cytotoxic T lymphocytes Cyp-B Cyclophilin B DAM Differentiation antigen melanoma (the epitopes of DAM-6 and DAM-10 are equivalent, but the gene sequences are different. DAM-6 is also called MAGE- B2 and DAM-10 is also called MAGE-B1) ELF2 Elongation factor 2 Ep-CAM Epithelial cell adhesion molecule EphA2, 3 Ephrin type-a receptor 2,3 Ets E-26 transforming specific (family of transcription factors) ETV6-AML1 Ets variant gene 6 / acute myeloid leukemia 1 gene ETS FGF-5 Fibroblast growth factor 5 FN Fibronectin G250 Glycoprotein 250 GAGE G antigen GnT-V N-Acetyl glucosaminyl transferase Gp100 Glycoprotein 100 kda HAGE Helicase antigen HER-2/neu Human epidermal receptor 2/neurological HLA-A*0201-R170I Arginine (R) to isoleucine (I) exchange at residue 170 of the a-helix of the a2- domain in the HLA-A2 gene H/N Head and neck HSP70-2 M Heat shock protein 70-2 mutated HST-2 Human signet-ring tumor 2 htert Human telomerase reverse transcriptase ice Intestinal carboxyl esterase IL-13Ra2 Interleukin 13 receptor a2 chain KIAA0205 Name of the gene as it appears in databases LAGE L antigen LDLR/FUT Low density lipid receptor / GDP-L-fucose:b-D-galactosidase 2-a-L-fucosyltransferase MAGE Melanoma antigen MART-1/Melan-A Melanoma antigen recognized by T cells-1 / melanoma antigen A MART-2 Melanoma Ag recognized by T cells-2 MC1R Melanocortin 1 receptor M-CSF Macrophage colony-stimulating factor gene MHC Major histocompatibility complex MSI Microsatellite instability MUC1, 2 Mucin 1, 2 MUM-1, -2, -3 Melanoma ubiquitous mutated 1, 2, 3 NA88-A NA cdna clone of patient M88 Neo-PAP Neo-poly(A) polymerase NPM/ALK Nucleophosmin/anaplastic lymphoma kinase fusion protein NSCLC Non small cell lung carcinoma NY-ESO-1 New York esophageous1 OA1 Ocular albinism type 1 protein OGT O-Linked N-acetylglucosamine transferase gene ORF Open reading frame OS-9 Name of the gene as it appears in databases P15 Protein 15 p190 minor bcr-abl Protein of 190-kDa bcr-abl Pml/RARa Promyelocytic leukemia / retinoic acid receptor a PRAME Preferentially expressed antigen of melanoma PSA Prostate-specific antigen PSMA Prostate-specific membrane antigen PTPRK Receptor-type protein-tyrosine phosphatase kappa RAGE Renal antigen RCC Renal cell carcinoma RU1, 2 Renal ubiquitous 1, 2 SAGE Sarcoma antigen SART-1, -2, -3 Squamous antigen rejecting tumor 1, 2, 3 SCC Squamous cell carcinoma SSX-2 Synovial sarcoma, X breakpoint 2 Survivin-2B Intron 2-retaining survivin SYT/SSX Synaptotagmin I /synovial sarcoma, X fusion protein TAA Tumor-associated antigen TEL/AML1 Translocation Etsfamily leukemia/acute myeloid leukemia 1 TGFbRII Transforming growth factor b receptor 2 TPI Triosephosphate isomerase TRAG-3 Taxol resistant associated protein 3 TRG Testin-related gene TRP-1 Tyrosinase-related protein 1, or gp75 TRP-2 Tyrosinase-related protein 2 TRP-2/INT2 TRP-2/intron 2 TRP-2/6b TRP-2/novel exon 6b TSTA Tumor-specific transplantation antigens WT1
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12 Immune reactions against tumor cells T cell mediated (CD8+, CD4+Th1, NK) macrophage mediated immunoglobulin mediated (ADCC) network of cytotoxic cytokines
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14 Tumor escape Over expression or down regulation of MHC-I. over expression of FcR deficiency of cytokine receptors production of different glycoproteins with masking effects
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17 Possible immuno-therapies immunotargeting through the TAAs Immunomodulation Cytokine therapy Tumor vaccines
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19 Recruitment of dendritic cells by DNA vaccine of GM-CSF
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21 Immunotoxin therapy
22 HER-2/neu
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24 Immunotoxin therapy of hairy cell leukemia with BL22
A listing of human tumor antigens recognized by T cells: March 2004
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