Table 5.

Summary of CAR T cell research questions

CAR construct delivery into the T cell	• Does gammaretroviral transduction of mature T cells mediate insertion into genetic sites that have been previously identified as oncogenic?• Are there methods of gene transfer other than viral transduction that can engineer a bulk product of CAR T cells within as short a period of time, such as 1 wk?• What are the CAR T production failure rates in trials that use lentiviral versus gammaretroviral CAR transduction?
Clinical trials in B cell malignancies	• Are there antigens other than CD19 that can be targeted with a CAR to mediate reproducible, efficacious, and safe outcomes in patients with cancer?• Why is B-ALL so much more sensitive to CD19-targeted CAR T cells than CLL or other NHL? Might it be tumor microenvironment or trafficking?• Do CAR T cells produced from patients with CLL or B-ALL differ in function?• Can conditioning chemotherapy be further optimized? Is chemotherapy the only option for conditioning before CAR T cell infusion?• With similar CR rates, is CAR T persistence required for durable remissions?• Why does 41BB-containing CAR T cells persist longer than CD28-containing CAR T cells?
Toxicities associated with CAR T cell therapy	• What cells are involved with the CRS? What cytokines do the cells produce?• Is there a cytokine or effector cell that contributes to CRS toxicity but not anti-tumor killing?• Do CAR T cells migrate to CNS in response to antigen or inflammation?• Does tocilizumab only work through inhibition of IL-6?