immunotherapy

Question 1

polyclonal antibodies

Answer 1

• mixture of heterogenous antibodies usually produced by diff B cells
• bind to many different epitopes of a single antigen (higher risk of binding to other cells instead of target antigen)

eg hep B immunoglobin
- prevent or make HBV injection less severe
- babies exposed to HBV during preganacy or at birth given injection of HBIG to protect them

eg IVIG
- body doesn’t make enough antibodies due to immunodeficiency
- prevent immune cells from attacking self antigens

Question 2

monoclonal antibodies

Answer 2

• generated by identical B cells
• only bind to same epitope of antigen

injection of desired antigen into animal. B cells isolated from animal’s spleen and fused with myeloma cell line, creating hybridomas (immortal)

Question 3

challenges to antibody immunotherapy

Answer 3

human anti-mouse antibodies (HAMA)
- antibodies produced by the human immune system in response to exposure to mouse-derived proteins or antibodies

consequences
- in diagnostic test, interference of HAMA can cause inaccurate results
- HAMA reduce efficacy of mouse-derived drugs or cause AE

Question 4

how to address HAMA challenge

Answer 4

1. chimerisation of mouse antibodies into human-mouse variants (25% mouse)
   - retains specificity for the target antigen from mouse antibody while minimising potential for an immune response in humans by using constant region on human
2. humanisation of mouse antibodies (10% mouse)
   - grafting complementarity- determining regions (variable regions responsible for antigen binding) from mouse antibody onto human antibody
3. make full human antibodies

Question 5

murine (100% mouse) ->
chimeric (25% mouse) ->
humanised (10% mouse) ->
human (0% mouse) ->

Answer 5

omab
ximab
zumab
umab

Question 6

adoptive immunotherapy \

Answer 6

selectively targets cells (eg infected cells or cancer), avoiding healthy cells

• involves DC, NK, T cells

NK: cell-mediated direct cytotoxcicity, ADCC, cytokine mediated: DC produce IL-12 to activate NK which secretes to activate macrophage to kill phagocytosed microbe , recognise change in surface molecules like downregulation of MHC class 1

T cell
- cytotoxic t cell -> recognise antigen presented on cancer cell through MHC class I
- tumour infiltrating lymphocytes -> migrate into tumour cell to kill like cytotoxic T cell `

Question 7

tumour immune escape stragies

Answer 7

loss of tumour specific antigens

loss or reduced expression of MHC class I

recruitment of immunosuppressive cells like Tregs

release of immunosuppressive factors like TGF-beta from the tumour

express inhibitory cell surface proteins like CTLA-4 and PDL1

Question 8

concept of adoptive immunotherapy

Answer 8

1) Collect immune cells from a patient and grow in the lab
2) put back the cultured immune cells into the patient to help immune system fight disease

Question 9

how NK cells differentiate tumour cells from healthy cells

Answer 9

MHC I on healthy cells stimulate negative signal in NK cell -> inhibit cell killing

but reduced/absent MHC I on tumour cells cannot stimulate sufficient negative signal in NK cell

Question 10

strategies of adoptive cancer immunotherapy

Answer 10

• DC vaccine -> expose DC to target antigen and polarise them to target antigens more effectively
• infusion of NK cells
• infusion of T cells expressing tumour antigen

types of adaptive cancer immunotherapy
- tumour infiltrating lymphocytes (TIL)
- CAR-T
- TCR therapy -> T cell engineered with TCR that targets tumour antigen