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31 Cards in this Set

  • Front
  • Back
Hallmarks of Cancer
-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
Extrinsic hallmark of cancer
avoidance of immunosurveillance
Cancer Immunosurveillance
phsyiologic function of immune system
recognize and destory clones of transformed cells before they grow into tumors
eradicate tumors after they have formed
CD8+ CTL Function
Lysis of tumor stromal fibroblasts, tumor cells, and tumor stromal endothelial cells
CD4+ T Helper Function
Prevent angiogenesis of tumor stromal fibroblasts, promote M2 Macrophages
IKDC Function
Promote tumor cell lysis, cross-presentation of tumor antigens, and prevent angiogenesis
NK Cell Function
Activated by BCR-ABL, IL-4 and IL-13, KIT inhibitors
Interact with inhibitory receptor on tumor cell
NKT Cell Function
Prevent angiogenesis, promote lysis of tumor cells
Gamma-delta Function
Promote lysis
Tumor-specific antibody function
Lysis, complement-mediated lysis, antibody-dependent cytotoxicity
Mechanisms of Escape from Immunosurveillance
Immune selection for non-immunogenic tumors
Myeloid suppressor cells (Tregs)
Immune selection
Immune selection develops at equilibrium for cells with decreased MHC Class I molecules and decreased IFNgamma response
Inhibit CD8+ proliferation
Promote CD4+ apoptosis
Suppressive mechanisms lead to T-cell arrest, anergy, apoptosis or APC apoptosis/dysfunction
TH2 shift
Suppression of tumor cell lysis
iDC and Tregs
Cause anergy of T cells
Tumor Dependent Factor
Promotes apoptosis
Promotes apoptosis and antigen uptake
Cancer Vaccines
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
Adaptive Cell Therapy
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
Gene Therapy:
technique for introducing genetic material of a gene into cells or patient
reverese genetic cause of cancer or progress of carcinogenic process
Viruses Used in Gene Therapy
Adeno-associated virus
-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
-highly immunogenic
-causes inflammation, anaphylaxis
Adeno-associated Virus
-chromosomal integration
-long-term expression
Ex Vivo Gene Therapy
Cells removed from body --> transgene delivered --> cells cultured --> cells returned to body
In Vivo Gene Therapy
Transgene delivered directly into host
rAAV Advantages
Activation of CTLs and Antibody responses
Ease of inserting foreign genes
At least 6 months, up to 2 years
Somatic Gene Therapy
Corrects cell populations or tissues
Germinal Gene Therapy
Whole "transgenic" organisms
Gene Vaccines
Mobilize normal human defenses against some tumor products
Non-viral Vectors
coat DNA with proteins
biodegradable polymers
gene gun
chemical/physical methods