CAR T cell therapy

Question 1

What is immunotherapy?

Answer 1

Treatment of a disease by activating the immune
system to attack the diseased cells.

Targeted therapy.

Can be highly specific.

Tissue/cell specificity.

Question 2

What is the mechanism of CAR T cell therapy?

Answer 2

After transplantation, CAR T-cells engraft and proliferate.

CARs recognise tumour antigen leading to killing of tumour cells.

Antigen release promotes host immune system.

Continued immune surveillance by persistence of CAR T-cells.

Question 3

What are the side effects of drugs that target CD19?

Answer 3

Side effects include cytokine release syndrome and neurotoxicity.

The causes of neurotoxicity is unclear.

Cytokine release syndrome (CRS) is an endogenous feature of CAR T-cells.

Alongside CAR T-cell therapy, immunosuppression is necessary e.g. tocilizumab (anti-IL-6 receptor antagonist) is used routinely to control CRS.

Question 4

What are some obstacles to CAR T-cell therapy?

Answer 4

Antigen escape:

Leukemia cells stop expressing the target antigen.
CD19 CAR T-cells can no longer recognise cancer cells.
Develop CAR T-cells that target multiple antigens e.g. CD19 and CD22 / CD37.

T-cell exhaustion:

Extended antigen stimulation can lead to progressive loss of effector functions.
Combining CAR T-cells with other immunotherapies that block exhaustion pathways.
e.g. checkpoint inhibitors that block PD-1/PD-L1 pathway.