First in-depth profile of CAR T-cell signals suggests how to improve immunotherapy

SEATTLE — Aug. 21, 2018 — CAR T-cell therapy, which reprograms immune cells to fight cancer, has shown great promise in people with some blood cancers who have not responded to other treatments. But until now, the underlying biological pathways enabling anti-cancer responses have not been thoroughly examined.

Understanding these pathways is important for designing future generations of CAR T-cell therapies, including reducing side effects, preventing post-treatment relapse, and making them effective against more-common cancers, such as solid tumors.

In a study published Aug. 21 in Science Signaling, researchers at Fred Hutchinson Cancer Research Center compared T-cell signaling patterns in two different designs of CARs, short for “chimeric antigen receptors,” using lab models. It’s the first profiling of its kind to compare two common CAR designs that are used in the clinic.

“The immunotherapy field has had an explosion of interest in the past few years as an emerging new pillar of cancer treatment, and there’s been a rush to test CAR T-cell therapies in the clinic,” said Dr. Stanley Riddell, lead author of the paper and the scientific director of the Immunotherapy Integrated Research Center at Fred Hutch.

“When we began this study in 2014, we sought to understand the biology of CAR


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