Immunotherapy 2

Question 1

Mechanism of immune checkpoint protein inhibition

Answer 1

1) co-stimulation i CD28 ligation trances T cell activating signs (when presented to MHC on APC)
2) CTLA-4 ligaton on activated T cell down-regulates T cell responses
3) blocking CTLA-4 legation enhances T cell response

Question 2

when CTLA-4 on T cell binds B7 on APC

Answer 2

no cell activation

Question 3

When anti-CTLA4 mAB blocks CTLA-4 from binding to B7

Answer 3

T cell activation

Question 4

example of an immune checkpoint proteins

Answer 4

CTLA4- keeps immune responses in check by preventing overly intense responses that might damage normal cells

Question 5

first drug used to modulate checkpoint proteins in immune response

Answer 5

Ipilimumab - treatment of advanced melanoma- blocks activity of CTLA4

Question 6

what activity does Ipilimumab block

Answer 6

CTLA4- means cannot complex with B7 on APC- enhancing T cell activation

Question 7

Immune Checkpoint Protein Inhibition Therapy

- Nivolumab

Answer 7

approved for patients with advanced melanoma or advanced lung cancer

Question 8

Immune Checkpoint Protein Inhibition Therapy

• pembrolizumab

Answer 8

approved for patients with advanced melanoma

Question 9

TGN1412 is called

Answer 9

Theralizumab

Question 10

TGN1412 was used as an

Answer 10

immuno-modulaotry frug for rheumatoid arthritiis

Question 11

how did TGN1412 work

Answer 11

binds to CD28 co-stimualtor pair on T cells

• potent agonist
• stimulation inflammatory production

-causes severe inflammatory reaction due to CYTOKINE RELEASE SYNDROME

Question 12

Adoptive Immune cell therapy: Normal TILs

Answer 12

Idea behind this approach is that the TILs have already shown the ability to target tumor cells, but there may not be enough of them within the tumour to eradicate it or overcome the immune suppressive signals that are being released there

Introducing massive amounts of activated TILs can help to overcome these barriers and shrink or destroy tumors

In some experimental cases these treatment responses
have lasted for years

Question 13

process of using normal TILs to treat tumour cells

Answer 13

• TILs are collected from samples of the tumour
• TILS that show the greatest recognition of the patients tumour in lab are selected
• cells are then activated with cytokines and unfused into the patients blood stream

Question 14

Transgenic TILs

Answer 14

T cells are engineered to have a specific transgenic TCR which we know has high affinity to a certain tumour antigen

Question 15

CAR-T Cells

Answer 15

Chimeric Antigen Receptor Modified T cells

Question 16

how does CAR-T cells therapy work

Answer 16

• a patients isolated T cell are collected for the blood and eugenically modified to express a protein known as CAR
• CARs are modified forms of T cell receptors- which are expressed on surface of T cell
• these receptors allow modified T cells to attach to specific proteins on the surface of cancer cells
• once bound to the cancer cells, the modified T cell come activated and attack the cancer cells
• modiife cells are grown in lab to produce large pop of cells and then res-infused into patients

Question 17

CARs are

Answer 17

are modified forms of T cell receptors- which are expressed on surface of T cell
- these receptors allow modified T cells to attach to specific proteins on the surface of cancer cells

Question 18

tumour antigen specific gene therapy by a gene-modified T lymphocyte: TCR

Answer 18

1) sensitive signal amplification derived by evolution
2) low avidity
3) targets intracellular proteasome
4) require MHC class I expression and HLA matching on tumour cell
5) possible mispairing with endogenous TCR

Question 19

tumour antigen specific gene therapy by a gene-modified T lymphocyte: CAR

Answer 19

1) signal amplification derived by synthetic biology
2) avidity controllable
3) targets only surface structures
4) HLA independent antigen recognition , universal application
5) no mis-pairing with endogenous TCR