cancer immunotherapy

Question 1

what types of monoclonal antibodies are used in cancer immunotherapy

Answer 1

1. conventional mabs
2. Drug antibody conjugates
3. Redirected T cells
4. checkpoint inhibitors

Question 2

what types of cancer vaccines are used in cancer immunotherapy

Answer 2

oncolytic viruses, vaccines

Question 3

what types of adoptive T cell transfer are used in cancer immunotherapy

Answer 3

1. tumour infiltrating lymphocytes (TILs)
2. Chimeric antigen receptors (CAR) T cells

Question 4

what are the ways that antibodies can kill tumour cells

Answer 4

1. Antibody-drug conjugates
2. Bispecific mABs
3. redirected T-cells
4. conventional mABs

Question 5

how do antibodies kill cells

Answer 5

1. signalling effects -> blocking downstream signalling
2. compliment lysis and opsonisation
3. ADCC by macrophages

Question 6

what is ritixumab

Answer 6

an anti-CD20, blocks a pathway and causes apoptosis

Question 7

what is herceptin

Answer 7

anti-Her2neu, used in breast cancer

Question 8

what is erbitux

Answer 8

anti-EGFR, anti proliferative, used in CRC and head and neck

Question 9

what is avastin

Answer 9

anti-VEGF, blocks growth of new blood supply, used in lung cancer

Question 10

Antibody-drug conjugates (ADCs)

Answer 10

1. v potent
2. travels in blood to tumour - linker must be stable to avoid releasing drug into blood and causing toxicity
3. conjugate binds to receptor on tumour
4. drug released in lysozyme

Question 11

Bispecific MAbs

Answer 11

1. target tumour
2. target T-cell (CD3 receptor)
3. administered via continuous infusion

Question 12

what happens in the elimination phase of cancer immunoediting

Answer 12

antibody-specific CD8/CD4 cells kill melanoma cells but not all which leads to equilibrium (cancer lays dormant)

Question 13

Nivolumab and pembrolizumab

Answer 13

both approved for melanoma and for NSCLC. used in combination but can be very toxic

Question 14

problems with checkpoint inhibitors and stimulators

Answer 14

1. work on all T cells not just cancer-specific ones and therefore they induce autoimmunity
2. only work if tumour has instigated an immune response

Question 15

which checkpoint inhibitors are effective in 20-50% of patients

Answer 15

Anti-CTLA-4 and anti-PD-1

Question 16

prophylactic vaccines

Answer 16

stimulate antibody response to prevent disease e.g. HPV. Stops virus entering cells and causing cancer

Question 17

therapeutic vaccines

Answer 17

stimulate T cell response to kill existing tumours

Question 18

process of therapeutic vaccines stimulating T cell response

Answer 18

1. stimulate de novo CD4 and CD8 T cell response
2. CD4+ or helper T cells reverse the immunosuppressive environment
3. CD8+ or killer T cells kill tumour cells directly

Question 19

problems with vaccines

Answer 19

1. stimulate potent T cells that overcome immunosuppressive env and kill tumours
2. T cells which recognise self-antigens may have been deleted

Question 20

T Vec vaccine

Answer 20

1. attenuated oncolytic virus
2. penetrates into tumour and proliferates which leads to cancer cell being overwhelmed

Question 21

what happens in adoptive T cell therapy

Answer 21

take T cell from tumour, expand it in lab and then give it back to person

Question 22

issues with adoptive T cell therapy

Answer 22

1. not off the shelf - must be personalised
2. low freq of tumour specific T cells