tumour immunology

Question 1

what is a positive PCD patient serum test and why?

Answer 1

peroxidase conjugates with antibodies to give a strong brown colour

Question 2

what incresases the risk of tumour malignancy?

Answer 2

immunesuppression

Question 3

give an example that would give the tumour cells an advantage over immune cells

Answer 3

if the tumour cells stop extressing MHC molecules

Question 4

what is the principle of checkpoint blockade?

Answer 4

Rather than directly stimulate responses, this approach seeks to reduce/remove negative regulatory controls of existing T cell responses

Question 5

what molecules are targeted in check point blockade

Answer 5

PD-L1/PD-1
CTLA4/B7.1
PD-L1/B7.1

Question 6

what are the Requirements for activation of an adaptive anti-tumour immune response

Answer 6

1. Local inflammation in the tumour (“danger signal”)

2. Expression and recognition of tumour antigens

Question 7

what are the problems with immune surveillance

Answer 7

1. It takes the tumour a while to cause local inflammation

2. Antigenic differences between normal and tumour cells can be very subtle (e.g. small number of point mutations)

Question 8

what is the function of MHC molecules?

Answer 8

present the contents of the cell for surveillance by T cells

Question 9

give some examples of cancers from viral origin

Answer 9

epstein Barr virus

Human papillomavirus

Question 10

what are tumour associated antigens?

Answer 10

Tumour-associated antigens (TAA) are normal cellular proteins which are aberrantly expressed (timing, location or quantity).

Because they are normal self proteins, for an immune response to occur tolerance may need to be overcome.

Question 11

give some examples of tumour associated antigens

Answer 11

human epidermal growth factor receptor 2 (HER2)

mucin 2 (MUC-1)

Carcinoembryonic antigen (CEA)

Question 12

what are the main problems with Targeting of tumour-associated auto-antigensfor T cell-mediated immunotherapy of cancer

Answer 12

1. Auto-immune responses against normal tissues
2. Immunological tolerance
   - Normal tolerance to auto-antigens
   - Tumour-induced tolerance

Question 13

what approaches are being used and developed for tumour immunotherapy?

Answer 13

1. Antibody-based therapy
2. Therapeutic vaccination
3. Immune checkpoint blockade
4. Adoptive transfer of immune cells
5. Combinations of 1) to 4) above

Question 14

give some examples of monoclonal antibody-based therapy

Answer 14

• ‘naked’ eg. trastuzumab anti HER2
• ‘conjegated’ radioactive protein eg. ibritumobab tioxetan anti CD20

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Question 15

give an example of a therapeutic cancer vaccination

Answer 15

Provenge® (sipuleucel-T) for advanced prostate cancer

Question 16

what is a risk of immune checkpoint blockade?

Answer 16

run the risk of causing autoimmune disease