T Cells Expressing Chimeric Antigen Receptors Can Cause Anaphylaxis in Humans

Cancer Immunology Research - Tập 1 Số 1 - Trang 26-31 - 2013
Marcela V. Maus1, Andrew R. Haas1, Gregory L. Beatty1, Steven Μ. Albelda1, Bruce L. Levine1, Xiaojun Liu1, Yangbing Zhao1, Michael Kalos1, Carl H. June1
1Authors' Affiliations: 1Abramson Cancer Center; Departments of 2Medicine and 3Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Tóm tắt

AbstractT cells can be redirected to overcome tolerance to cancer by engineering with integrating vectors to express a chimeric antigen receptor (CAR). In preclinical models, we have previously shown that transfection of T cells with mRNA coding for a CAR is an alternative strategy that has antitumor efficacy and the potential to evaluate the on-target off-tumor toxicity of new CAR targets safely due to transient mRNA CAR expression. Here, we report the safety observed in four patients treated with autologous T cells that had been electroporated with mRNA coding for a CAR derived from a murine antibody to human mesothelin. Because of the transient nature of CAR expression on the T cells, subjects in the clinical study were given repeated infusions of the CAR-T cells to assess their safety. One subject developed anaphylaxis and cardiac arrest within minutes of completing the third infusion. Although human anti-mouse immunoglobulin (Ig)G antibodies have been known to develop with CAR-transduced T cells, they have been thought to have no adverse clinical consequences. This is the first description of clinical anaphylaxis resulting from CAR-modified T cells, most likely through IgE antibodies specific to the CAR. These results indicate that the potential immunogenicity of CARs derived from murine antibodies may be a safety issue for mRNA CARs, especially when administered using an intermittent dosing schedule. Cancer Immunol Res; 1(1); 26–31. ©2013 AACR.

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Cancer Immunology Research

Tập 1 Số 1

26-31

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