{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:14:14Z","timestamp":1793164454618,"version":"4.5.0"},"reference-count":140,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,1,8]]},"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:p>Despite promising clinical results in a small subset of malignancies, therapies based on engineered chimeric antigen receptor and T-cell receptor T cells are associated with serious adverse events, including cytokine release syndrome and neurotoxicity. These toxicities are sometimes so severe that they significantly hinder the implementation of this therapeutic strategy. For a long time, existing preclinical models failed to predict severe toxicities seen in human clinical trials after engineered T-cell infusion. However, in recent years, there has been a concerted effort to develop models, including humanized mouse models, which can better recapitulate toxicities observed in patients. The Accelerating Development and Improving Access to CAR and TCR-engineered T cell therapy (T2EVOLVE) consortium is a public\u2013private partnership directed at accelerating the preclinical development and increasing access to engineered T-cell therapy for patients with cancer. A key ambition in T2EVOLVE is to design new models and tools with higher predictive value for clinical safety and efficacy, in order to improve and accelerate the selection of lead T-cell products for clinical translation. Herein, we review existing preclinical models that are used to test the safety of engineered T cells. We will also highlight limitations of these models and propose potential measures to improve them.<\/jats:p>","DOI":"10.1136\/jitc-2021-003486","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T13:30:37Z","timestamp":1653312637000},"page":"e003486","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Time to evolve: predicting engineered T cell-associated toxicity with next-generation models"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-7254","authenticated-orcid":false,"given":"Emmanuel","family":"Donnadieu","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris, Institut Cochin, INSERM, CNRS, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Luu","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik II, Universit\u00e4tsklinikum W\u00fcrzburg, 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