Cancer Treatment: Immunotherapy

Question 1

What are the types of cancer immunotherapy

Answer 1

• Monoclonal antibodies
• vaccines
• adoptive T cell trasnfer

Question 2

types of monoclonal antibodies

Answer 2

• conventional mabs
• drug-antibody conjugates
• bispecific mabs
• redirected T cells
• checkpoint inhibitors

Question 3

conventional mabs

Answer 3

• opsonisation
• signalling, leading to apoptosis or growth arrest, ADCC (antibody-derived cellular cytosis)

Question 4

approved conventional mabs

Answer 4

• rituximab: anti-CD20, non-hodgkins lymphoma, heamatological cancers
• herceptin: anti-Her2, breast cancer
• erbitux: anti-EGFR, adv CRC
• avastin: anti-VEGF, adv CRC

Question 5

antibody-drug conjugates

Answer 5

• potent drug (topoisomerase inhibitors) attached by linker to antibody
• travels in blood to tumour
• link must be STABLE to avoid release into blood
• binds to receptor on tumour and drug is internalised and released in lysozyme
• kills tumour cell

Question 6

ADC examples

Answer 6

• Kadcycla- 2017- metastatic breast cancer
• T-Dxd- 2021- breast cancer- HER2 overexpressed
• Sacituzumab govetican- triple negative breast cancer targeting Trop-2

Question 7

bi-specific mabs: catumaxomab

Answer 7

• two different antigen binding sites created via genetic engineering
• one antigen recognises tumour and other recognises T cell
• T cell kills tumour
• can still perform normal functions like ADCC

Question 8

bi-specific mabs: blinotumomab

Answer 8

• B cell leukeamia/lymphomas
• engineer binding site of scFv then link two together
• potent activity
• small, easy production
• no Fc so no effector function
• rapidly excreted so low amount reach tumour
• continuous IV

Question 9

CTLA4 targeting antibody

Answer 9

• CTLA4 prevents over-stimulation of T-cells, and inactivates them
• antibodies bind to this proteins and prevent T-cell inactivation

Question 9

cancer and the immune system

Answer 9

• immunogenic cancers (eg. melanoma) have a LATENT period
• elimination: no cancer, mutated cells removed by immune system
• equilibrium: mutations allow cells to avoid immune system but immune system adapts, so latent
• escape: cancer evolves quicker than immune system can adapt, causing a visible cancer

Question 10

Anti-Pd1

Answer 10

• stops cancer cells from evading death from T-cells
• allows secretion of interferon gamma from t-cells
• treatment of melanoma

Question 11

checkpoint inhibitors

Answer 11

• they work on all t cells not just cancer specific t cells
• induce autoimmunity
• ONLY work if tumour has instigated an immune response
• anti-CTLA4/Pd1 very effective in 25-50%
• not clear if others will be as successful

Question 12

prophylactic vaccines

Answer 12

stimulates antibody response to prevent disease, eg. HPV vaccine prevents development of cervical/head and neck cancer
needs to be given BEFORE exposure so well before cancer has developed

Question 13

therapeutic vaccines

Answer 13

• stimulate T-cells response to kill existing tumours
• stimulate CD4 (helper) and CD8 (killer) T-cells
• none of these exist yet
• difficult to penetrate TME

Question 14

oncolytic viruses

Answer 14

• T-vec
• modified virus (Herpes) inhected into tumour
• virus replication kills tumour cells
• also recruits other immune cells to become APCs
• need to have accessible tumour (melanoma)
• very good response in injected lesion BUT weaker response for metastases
• stage 4 melanoma

Question 15

mRNA personalised vaccines

Answer 15

• moderna technology
• give patient the mRNA to trigger cancer recognition and immune system response
• works in melanoma patients

Question 16

adoptive T-cell therapy

Answer 16

• collect T cells from tumour ressection
• expand them
• identify reactive t cells (ie. respond to tumour)
• clone theze
• return to patient
• need highly specialised lab technology and takes time/money

Question 17

CARS

Answer 17

• blood cancers
• doesn’t rely on MHC so works for everyone
• VERY expensive, so only used when other options are exhausted