Immunotherapy of cancer Flashcards
what are the 3 E’s used to describe immunoediting
Elimination
Equilibrium
Escape
Elimination
Nk, NKT, Macs and DCs(innate)
INF gamma and chemokines lead to tumour death
tumour specific DCs activate adaptive immunity in draining lymph nodes
tumour specific CD4+ and CD8+ T cell join
Equilibrium
Elimination phase is incomplete
tumour cells lies dormant and modulate tumour antigen expression and stress signals
the immune system eliminates susceptible tumour clones when possible sufficient to prevent tumour expression
tumour heterogeneity resulting in Darwinian selection
Escape
immune system is unable to control the tumour growth leading to tumour progression
BCG
bacillus calmette -Guerin vaccine for TB good immunological adjuvant stimulates the innate immune system TLR's used in bladder cancer-intravascular injection
Cytokines (Interferon)
Type 1 interferon (a and b)
produced by virally infected cells
viral detection pathway within most cells
upregulate MHC class1, tumour antigen and adhesion molecule
activates T cells, B cells and Dc
used successfully in metastatic melanoma
Nasty side effects (flu like symptoms )
Cytokines (interleukin-2)
T cell growth factor
success in RCC and melanoma
toxicity
LAK cells, PMBC treated with IL-2 and re-infused into patients
Cytokines (GM-CSF)
GM-CSF stimulate APC
Trialled in melanoma, evidence of some success
May be of benefit if used in conjunction with IL-2
what does Trastuzumab (Herceptin) target
target ERBB2 (human epidermal growth factor) on breast cells. Blocks ERBB2 signalling and allows targeting of ADCC
what bevacizumab (Avastin) target
targets VEGF and block signalling. Used against colon cancer, NSCLC, glioblastoma and kidney cancer.
Apoptosis induction
rituximab : anti-CD20 , used for CD20 positive B cell Non-Hodgkin’s lymphoma and chronic lymphocytic lymphoma.
Alemtuzumab(campath): an anti CD52, used B-CLL
immunomodulation
ipilimumab (anti CTLA-4 , Block the inhibition due to CTLA-4 signalling
used in metastatic melanoma
