immunotherapy of cancer

Question 1

what does imbalance in immune system lead to

Answer 1

immunodeficiency lead to tumour formation

inflammatory conditions lead to cancers too

Question 2

tumour immunosurveillance

Answer 2

process where the immune system, namely lymphocytes, recognise cancerous and pre-cancerous cells lead to elimination before they can cause damage

Question 3

tumourigenesis

Answer 3

normal cells undergoing change
develop abnormal tumour antigens
danger signals such as extra-cellular matrix products

Question 4

describe elimination

Answer 4

NKs, NKTs, Macs and DC
INFy and chemokines lead to tumour death
tumour specific DCs activate adaptive immunity in draining lymph nodes
tumour specific CD4+ and CD8+ T cells join

Question 5

equilibrium

Answer 5

elimination phase is incomplete

tumour cells lie dormant and may modulate tumour antigen expressions and stress signals

immune system eliminates susceptible tumour clones when possible sufficient to prevent tumour expanison

tumour heterogeniety resulting in darwinian selection

Question 6

escape

Answer 6

immune system is unable to control the tumour growth leading to tumour progression

Question 7

interferon

Answer 7

type I
produced by virally infected cells
viral detection pathways within most cells
upregulates MHC class I, tumour antigens and adhesion molecules
activates t , b and DC cells
used successfully in metastatic melanoma
nasty side effects = flu like symptoms

Question 8

interleukin 2

Answer 8

t cell growth factor
success in RCC and melanoma
toxicity
LAK cells,

Question 9

GM-CSF

Answer 9

stimulates antigen presenting cells
trialled in melanoma, evidence of some success
may be benefit if used in conjunction with IL-2

Question 10

blockade of growth factors

Answer 10

trastuzumab = targets erbb2 on breast cancer cells. blocks ERBB2 signalling and allows targetting of ADCC

bevacizumab targets VEGF and blocks signalling. used against colon cancer, NSCLC, glioblastoma and kidney cancer

Question 11

apoptosis induction

Answer 11

rituximab = used for cd20 positive b cell non hodgkin lymphoma and chronic lymphocytic lymphoma

alemtuzumab = anti cd52, used for b-cll

Question 12

checkpoint inhibition

Answer 12

blockade of effector cell death 
antibody against PD-1 
expressed on T cells and can induce apoptosis when bound by PDL-1
PDL-1 can be found on tumour cells 
nivolumab and pembrolizumab 
combination therapy with ipilimumab

Question 13

lymphokine activated killers

Answer 13

PBMC taken from patients and cultured with IL-2 
heterogenous population 
NK, NKT and T cells 
predominantly NK cells 
higher than normal anti-tumour activity 
can target nK resistant tumour cells

Question 14

natural killer cells

Answer 14

recognise lack of MHC1
about 5-10% of human peripheral blood lymphocytes 
majority are CD3-CD56+
found in blood, BM, spleen and liver 
main cell type in LAK populations