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31 Cards in this Set
- Front
- Back
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Hallmarks of Cancer
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-provide own growth signals
-ignore growth-inhibitory signals -avoid cell death -replicate w/o limits -sustain angiogenesis -invade tissues through basement membrane and capillary walls -avoidance of immunosurviellance |
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Extrinsic hallmark of cancer
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avoidance of immunosurveillance
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Cancer Immunosurveillance
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phsyiologic function of immune system
recognize and destory clones of transformed cells before they grow into tumors eradicate tumors after they have formed |
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CD8+ CTL Function
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Lysis of tumor stromal fibroblasts, tumor cells, and tumor stromal endothelial cells
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CD4+ T Helper Function
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Prevent angiogenesis of tumor stromal fibroblasts, promote M2 Macrophages
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IKDC Function
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Promote tumor cell lysis, cross-presentation of tumor antigens, and prevent angiogenesis
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NK Cell Function
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Activated by BCR-ABL, IL-4 and IL-13, KIT inhibitors
Interact with inhibitory receptor on tumor cell |
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NKT Cell Function
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Prevent angiogenesis, promote lysis of tumor cells
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Gamma-delta Function
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Promote lysis
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Tumor-specific antibody function
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Lysis, complement-mediated lysis, antibody-dependent cytotoxicity
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Mechanisms of Escape from Immunosurveillance
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Immune selection for non-immunogenic tumors
Myeloid suppressor cells (Tregs) |
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Immune selection
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Immune selection develops at equilibrium for cells with decreased MHC Class I molecules and decreased IFNgamma response
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Tregs
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Inhibit CD8+ proliferation
Promote CD4+ apoptosis Suppressive mechanisms lead to T-cell arrest, anergy, apoptosis or APC apoptosis/dysfunction |
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TH2 shift
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Suppression of tumor cell lysis
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iDC and Tregs
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Cause anergy of T cells
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Tumor Dependent Factor
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Promotes apoptosis
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TGF-Beta
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Promotes apoptosis and antigen uptake
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Cancer Vaccines
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Whole Tumor Cells
Plasmid DNA Defined tumor antigens Recombinant viral vectors Provide anti-tumor immunity (antigen specific) Can cause auto-immune damage to normal tissues |
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Adaptive Cell Therapy
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Tumor excision --> cultures with IL-2 --> test for IFNgamma production --> rapid clonal expansion with IL-2 and CD3 Antibody --> adaptive transfer of anti-tumor lymphocytes
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Gene Therapy:
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technique for introducing genetic material of a gene into cells or patient
reverese genetic cause of cancer or progress of carcinogenic process |
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Viruses Used in Gene Therapy
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Retrovirus
Adenovirus Lentivirus Adeno-associated virus |
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Retrovirus
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-activates proto-oncogene by insertional mutagenesis
-contaminated wild-type retrovirues cause lymphoma transgene inactivation in vivo -easily inactivated -must incubate target cells with producer cells for high transduction |
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Adenovirus
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-episomal
-transient -highly immunogenic -causes inflammation, anaphylaxis |
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Adeno-associated Virus
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-non-pathogenic
-chromosomal integration -long-term expression -safe |
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Ex Vivo Gene Therapy
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Cells removed from body --> transgene delivered --> cells cultured --> cells returned to body
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In Vivo Gene Therapy
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Transgene delivered directly into host
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rAAV Advantages
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Safe
Activation of CTLs and Antibody responses Ease of inserting foreign genes At least 6 months, up to 2 years |
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Somatic Gene Therapy
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Corrects cell populations or tissues
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Germinal Gene Therapy
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Whole "transgenic" organisms
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Gene Vaccines
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Mobilize normal human defenses against some tumor products
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Non-viral Vectors
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liposomes
coat DNA with proteins biodegradable polymers gene gun chemical/physical methods |
