CAR-TCR Engineering

Question 1

Engineering and usage of CAR T cells for therapy

Answer 1

• When CAR binds to a tumor cell through the extracellular/binding domain, it promotes a signaling response that activates a T cell and drives it to kill the tumor cell
• CAR is usually introduced by lentivirus
• All CARs are against lymphomas or myelomas (liquid cancers)

-Engineering: to make a CAR-T cell most potent and safe
- Rational design of signaling domains
- Small aa mutations to introcellular signaling domains or ITAMs
- Fine tuning of scFv region for higher affinity to antigen
- High throughput engineering

Question 2

Name a possible synthetic biology method to assure safety of CARs

Answer 2

• Next generation CAR-T cells include co-stimulatory domains that drive safety and improve efficacy, they avoid hyperimmune response that leads to cytokine storm.
• Adding a chimeric co-receptor next to the CAR -> parallel CAR. This co-receptor has only a co-signaling domain (no CD3-zeta), T cell overactivation is avoided