Nicole Brown (URCAD)

Cancer is the leading cause of death worldwide, with the number of cases expected to rise in the coming decades. While treatments are available, cancer immunotherapy is a major focus of research. One promising approach is chimeric antigen receptor (CAR) T cell therapy, a type of adoptive cell therapy that genetically modifies T cells to target specific antigens present on tumors. This therapy has shown success in treating blood cancers; however, the choice of targets for some malignancies is limited by the availability of ‘tumor specific’ antigens that are expressed only on tumors and not healthy tissues. When a CAR-T cell therapy is designed, it targets a tumor antigen that is also expressed in some normal tissues. We reasoned that safety could be improved using inducible gene systems that can control CAR gene expression in CAR-T cells and regulate activity. In this context, we are exploring the use of a humanized “receptor” which binds FDA-approved drugs which selectively activate “receptor”, effectively controlling CAR-T cell activity. This study describes a first-in-class fully human inducible gene expression system. These data suggest a novel method for regulating gene expression in CAR-T cell therapies, thereby eliminating potential side effects associated with on-target, off-tumor activity.