Car T Cellular Therapy

Question 1

Importance of T cell signaling (2)

Answer 1

1. Regulate T cells effector function, memory, cell proliferation and differentiation
2. TWO concurrent signals needed for full activation

Question 2

Immunotherapy strategies for TAA and TSAs

Answer 2

• oncolytic viruses, monoclonal antibodies, check-
  point inhibitors, cancer vaccines
• CAR T CELLS

Question 3

Tumor specificity of CAR T cells result from…

Answer 3

Tumor specificity of CAR T cells result from incorporation of an scFv
- binds TSA or TAA on surface of cancer cells are due

scFV = single-chain variable fragment

Question 4

CAR T Cell Manufacturing

Answer 4

• CAR DNA is engineered
• Incorporate CAR DNA in a carrier vector
• vector inserted into “virus-producer cell” to incorporate CAR DNA into a virus*
• CAR DNA incorporated into virus genome = CAR protein is translated = CAR T cell

*NOTE: = virus infects T cell but cannot replicate itself (modified retro/lenti-virus)

Question 5

CAR T Cell Therapy

Answer 5

• remove blood (T cells) from patient
• make CAR T cells in the lab = multiply
• infuse CAR T cells into patient
• CAR T cells bind cancer cells and kill them

Question 6

Describe: Ideal CAR-T target

Answer 6

• Tumor-specific
• universally expressed only on tumor cells; NOT on self
• self-surface molecule; NOT intracellular
  Ie. CD19 in B cells

Question 7

CAR T Cellular Therapy Toxicity

Answer 7

• cytokine release syndrome
• neurological toxicity
• on-target, off-tumor toxicity
• insertional oncogenesis
• anaphylaxis/ allergy

Question 8

Cytokine Release Syndrome

Answer 8

• systemic inflammatory response (elevated cytokines ie. IFN-y, IL-10, IL-6) = high fever, fatigue, tachycardia
• more intense in high tumor burden (tumor receptors)

Question 9

Neurological Toxicity

Answer 9

• confusion, delirium, aphasia*, seizure
• associated with Cytokine Release Syndrome

*NOTE: can’t talk/ comprehend language

Question 10

“On-target, off tumor” toxicity

Answer 10

• non-targeted attacks
• engagement of target antigen on non-pathogenic tissue (TAA)

Question 11

CAR T: pros vs cons

Answer 11

CAR T
Pro:
- non-HLA restricted
- targets non-peptide antigens
- higher affinity for immunoglobulin binding
- in vivo persistence

Cons:
- cannot target intracellular pathogens
- TAA evades CAR T
- T cell infusion toxicity
- cost of bio-manufacturing and transplant
- patient must be well enough to undergo process