Cell therapies for cancer: CAR-Ts in development
T cell based therapies, including T cell engaging bispecific antibodies, and genetically engineered chimeric antigen receptor engineered T cells (CAR-T cells) have produced remarkable results in clinical trials – achieving complete remissions in patients with hematological malignancies who failed multiple lines of prior therapy. Towards increasing the potency and safety of these therapeutics, as well as expanding them to cancers outside of the hematological space, we have defined how the biophysical characteristics of the antibody-based components of these therapies modulate the physiological response of the T cells that carry out the anti-tumor activity. For example, we have designed a “switchable” CAR-T cell system using antibody-based molecular switches. This platform enables fully tunable control of CAR-T cell activity in a universal format that can be redirected to nearly any therapeutic antigen target. The platform is expected to reduce the risk of severe adverse events that have plagued the development of CAR-T cell therapies clinically. We have demonstrated such a platform can reduce risks related to cytokine release syndrome and double as a safety switch to turn the therapy off in the case of an adverse event. We have further demonstrated the temporal control over CAR-T cell activation enables the development of robust central memory T cells. In preclinical mouse models we’ve demonstrated these central memory cells can be recalled affording on-demand, in vivo T cell expansion. These concepts are expected to be central to clinical efficacy with T cell based therapeutics and important to ultimately achieving efficacy in solid tumors. A proof of concept clinical trial will be initiated in late 2019 for patients with lymphoma.