The making and function of CAR cells.

The making and function of CAR cells. Immunol Lett. 2019 Jun 07;: Authors: Zabel M, Tauber PA, Pickl WF Abstract Genetically engineered T cells expressing chimeric antigen receptors (CAR) present a new treatment option for patients with cancer. Recent clinical trials of B cell leukemia have demonstrated a response rate of up to 90%. However, CAR cell therapy is frequently accompanied by severe side effects such as cytokine release syndrome and the development of target cell resistance. Consequently, further optimization of CARs to obtain greater long-term efficacy and increased safety is urgently needed. Here we high-light the various efforts of adjusting the intracellular signaling domains of CARs to these major requirements to eventually obtain high-level target cell cytotoxicity paralleled by the establishment of longevity of the CAR expressing cell types to guarantee for extended tumor surveillance over prolonged periods of time. We are convinced that it will be crucial to identify the molecular pathways and signaling requirements utilized by such 'efficient CARs' in order to provide a rational basis for their further hypothesis-based improvement. Furthermore, we here discuss timely attempts of how to: i) control 'on-tumor off-target' effects; ii) introduce Signal 3 (cytokine responsiveness of CAR cells) as an important building-block into the CAR concept; iii) most efficiently eliminate CAR cells once full remission has been obt...
Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research