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April 2019 Research Update

The Scaled Back Tale of CAR-based Therapeutics

Earlier this year, scientists from Sloan Kettering University reported in Nature Medicine1 that attenuating the activation potential of CD28-based chimeric antigen receptors (CARS) may actually improve the clinical outcome for patients with leukemias and lymphomas.

CAR-based therapy is just one of many immunotherapies to enter clinical trials in recent years. It works by engineering the patient's own T cells to enhance the immune response against a specific tumor antigen.

Despite early success in patients with leukemia and lymphoma, the limited persistence this therapy confers on T cells has been recognized as one of its constraints.

"Strong T cell activation drives exhaustion, which may be accentuated by the redundancy of CD28 and CD3ζ signaling, as well as the spatiotemporal constraints imparted by the structure of second-generation CARs," the authors explained.

Specifically, CARs designed with the functional ITAM at the first position exceeded the parent design by inducing long-term remission in...


1Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency: Nature Medicine 25, 82-88 (2019)

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Zone In With The Zon Blog Post

DNA Day 2019-April 25

The now iconic double-stranded helical structure of DNA was proposed by James D. Watson & Francis H. C. Crick in their famous publication in Nature on April 25, 1953, titled Genetic Implications of the Structure of Deoxyribonucleic Acid. This extremely brief report-only one page and one figure-contains what is arguably the most understated and brief, only one sentence-conclusion from base-pairing of...

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