why immunotherapy?

Question 1

who first noted appearance of leukocytes in solid tumours?

Answer 1

Virchow

Question 2

first evidence that T cells can constitutively kill cancer cells

Answer 2

• First evidence = graft-versus-tumour effect, observed following HSCT

• Donor T cells carried over into the recipient mount an immune response against remaining tumour cells in haematopoietic cancer patients
• Weiden et al (1979) = found that GVHD was associated with a powerful anti-tumour effect in leukaemia patients, with the leukaemia relapse rate 2.5-fold lower in transplant patients that experienced GVHD than those who did not

Question 3

evidence that adaptive immune system is important in tumour defence

Answer 3

• Veselv et al (2011) = adaptive immune system is important in tumour prevention

• Injected mice with carcinogen = fraction of mice developed tumours
• Then injected some of remaining healthy mice with antibodies depleting various cells in innate and adaptive immune system
• Mice in which adaptive immune system was impaired (through administration of anti-CD4, CD8, IL-12, IFNy antibodies), but not other animals went on to develop tumours

Question 4

approaches for immunotherapy

Answer 4

boost endogenous, tumour-specific T cell responses = CIs, neoantigen vaccines, ex vivo expansion of TILs

Stimulate cancer killing by endogenous non-tumour specific T cells = BITES, ImmTacs

used modified exogenous T cells = CAR T cell therapies