Exam 4 Cell-based Therapeutics 2

Question 1

What is the mode of action of cell-based therapies with immune cells?

Answer 1

1. adoptive transfer of cells, locally or systemically
2. can be engineered (CAR based) or non engineered
3. often done with cytokines to enhance cell persistence
4. killing occurs by either native killing or by direct targeting of single (or multiple) tumor antigens → example can be the release of proteins and granules that kill the cancer cells
5. off-switches (suicide genes to prevent over-activation of immune cells) may be needed

Question 2

Which administration has been approved by the FDA?

Answer 2

systemic

Question 3

What are some things to know about systemic administration?

Answer 3

1. easier
2. suitable for blood cancers and metastatic disease
3. risks off-target toxicities and higher risk for side effects
4. potential loss of specificity
5. less invasive
6. has a higher concentration for solid tumors

Question 4

What are some things to know about local administration?

Answer 4

1. more suitable for many solid cancers
2. fewer off target effects
3. many tumors are difficult to access
4. very invasive (such as injected straight to the brain)
5. example is for brain tumors

Question 5

What are cytokines?

Answer 5

proteins that support activation, maturation, and effector functions

Question 6

Why are immune cells infused with cytokines?

Answer 6

if cells are infused without cytokines, there is no support so the cells will die in a week but if they are infused with cytokines, the cytokines will stimulate the cells to not die

Question 7

What cells stimulate immune cells?

Answer 7

interleukins → won’t kill as much without cytokines

Question 8

What are the functions of the different cytokines?

Answer 8

each cytokine has different effects (but most are for the expansion process) → IL-2 promotes active cytotoxic T cells while IL-21 helps T cells for persistence and memory

Question 9

What is important to note about IL-2?

Answer 9

is the most common cytokine (can even be standalone therapy) → but can be very toxic

Question 10

How do immune cell drugs persist in vivo after infusion?

Answer 10

1. when cells are put into the body without genetically engineering, the cells will expand through antigen presentation
2. with CAR T cell expansion, cells are activated with cytokines and antibodies (CD3/CD28) to make cells super potent so that the cells live with the patient → ADME will be different

Question 11

What are the two clinical responses to CAR-T therapy?

Answer 11

1. lymphoma CD19-immunotherapy → after 1 infusion of CAR T cells, most of the cancer cells are gone →→ involves suicide switch! where patient gets small molecule to bind to suicide gene and switch it off → CAR activity is low and won’t kill the cells
2. eradication of leukemia in patient treated with chemotherapy followed by anti-CD19 CAR-T therapy →→ B cells make antibodies but express CD19 (cancer cells also express CD19) so the therapy can kill cancer cells and B cells → patient can no longer make antibodies anymore