IMMUNUOLOGY 2 - VACCINES AND CANCER THERAPY

Question 1

Tumourgenesis

Answer 1

Normal cells undergoing change
Develop abnormal tumour antigens
Danger signals such as extra cellular matrix products

Question 2

Elimination in cancer

Answer 2

Involve cells of innate system - NK cells, NKTs, DCs - INFγ and chemokines lead to tumour death.
Tumour specific DC activate adaptive immunity - draining lymph nodes
Tumour specific CD4 and CD8 T cells join

Question 3

Equilibrium in cancer

Answer 3

Elimination phase is incomplete - tumour cells evade parts of immune system
Tumour cells lie dormant - modulate tumour antigen expression and stress signals.
Immune system eliminate susceptible tumour clones - prevent tumour expansion - darwinian selection

Question 4

Escape in cancer

Answer 4

Immune system is unable to control the tumour growth = tumour progression

Question 5

Immunomodulation - Interferon

Answer 5

Type I interferon - produced by virally infected cells - viral detection pathways in most cells
Upregulate MHC I, tumour antigens and adhesion molecules
Activate T cells, B cells and DC - use in metastatic melanoma

Question 6

Immunomodulation - IL-2

Answer 6

T cell growth factor - success in RCC and melanoma
Toxicity
LAK cells, PBMC treated with IL-2 and re-infused into patients - decrease toxicity

Question 7

Immunomodulation - GM-CSF

Answer 7

Stimulate APC - trialled in melanoma, evidence of some success - maybe beneficial use with IL-2

Question 8

Immune mediated tumour cell killing

Answer 8

Antibodies expose Fc receptors to macrophage = macrophage destroys cell
Fc binds to complement = membrane attack complex
NK cells have Fc receptor - activate NK cells = ADCC
Antibodies bind to tumour material - take up by DC 0 present to T cells = CD4/CD8 cells
Anti CTLA4 antibody = T cell function longer

Question 9

What can block growth factors for cancer immunotherapy

Answer 9

Trastuzmab - herceptin

Bevacizumab - Avastin

Question 10

Trastuzmab function/mechanism for cancer immunotherapy

Answer 10

Trastuzumab (Herceptin) target ERBB2 on breast cancer cells - block ERBB2 signalling and allow targeting of ADCC

Question 11

Bevacizumab function/mechanism for cancer immunotherapy

Answer 11

Bevacizumab (Avastin) targets VEGF and blocks signalling – used against colon, kidney cancer

Question 12

What is used for apoptosis induction for cancer immunotherapy

Answer 12

Rituximab - anti CD20 - CD20 positive B cell non-hodgkins lymphoma and chronic lymphocytic lymphoma
Alemtuzumab - anti CD52 used for B-CLL

Targets all B cell not just tumours

Question 13

Anti CTLA4 function/mechanism for cancer immunotherapy

Answer 13

Ipilimumab - block inhibition due to CTLA-4 signalling - use metastatic melanoma
Problem = non-specific actions - immune related adverse events - skin and GI - treat with corticosteroids