Research ArticleCancer

CD3 bispecific antibody–induced cytokine release is dispensable for cytotoxic T cell activity

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Science Translational Medicine  04 Sep 2019:
Vol. 11, Issue 508, eaax8861
DOI: 10.1126/scitranslmed.aax8861

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Taming the cytokine beast

Bispecific antibodies, which are engineered to engage a cancer cell antigen and activate T cells to kill the cancer cell, are showing clinical promise. Unfortunately, they can also cause major side effects as a result of uncontrolled immune activation and cytokine release. Li et al. found a way to separate the beneficial effects from the harmful ones by showing that activation of tumor necrosis factor–α signaling is necessary for the toxic systemic cytokine release but not for successful cancer treatment. The authors identified several ways to inhibit the dangerous signaling pathway and demonstrated them in mouse models, with no loss of anticancer efficacy.

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