Remote control of therapeutic T cells through a small molecule–gated chimeric receptor

Chia-Yung Wu, Kole T. Roybal, Elias M. Puchner, James Onuffer, Wendell A. Lim

Science · 2015 · 663 citations · 43 references

DOIFull text

Open access

TL;DR

Redirecting the immune system to attack tumor cells is an effective cancer therapy, but engineered T cells risk runaway activity or off‑target effects that can be deadly. The study designs T cells with chimeric antigen receptors that include an additional control system. The control system allows clinicians to turn the engineered T cells on or off by administering a small molecule that, together with tumor antigen, activates their cytotoxic function. Wu et al., Science, 2023, DOI 10.1126/science.aab4077.

Abstract

Keeping a leash on cancer-killing cells Redirecting the immune system to attack tumor cells is proving to be an effective therapy against cancer. However, when patients are exposed to T cells engineered to recognize and attack cancer cells, there is a risk of runaway or excessive activity or of off-target effects, both of which can themselves be deadly. Wu et al. designed T cells expressing chimeric antigen receptors that recognize and attack cancer cells with an additional control system. This mechanism would allow a doctor administering the therapy to turn the engineered T cell “on” or “off” by administering a small molecule that is required along with cancer cell antigen to stimulate the T cells and activate their tumor cell–killing properties. Science , this issue p. 10.1126/science.aab4077

References

43