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Time to evolve: predicting engineered T cell-associated toxicity with next-generation models

Donnadieu, Emmanuel; Luu, Maik; Alb, Miriam; Anliker, Brigitte; Arcangeli, Silvia; Bonini, Chiara; De Angelis, Biagio; ... Casucci, Monica; + view all (2022) Time to evolve: predicting engineered T cell-associated toxicity with next-generation models. Journal for ImmunoTherapy of Cancer , 10 (5) , Article e003486. 10.1136/jitc-2021-003486. Green open access

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Abstract

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-private 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.

Type: Article
Title: Time to evolve: predicting engineered T cell-associated toxicity with next-generation models
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jitc-2021-003486
Publisher version: http://dx.doi.org/10.1136/jitc-2021-003486
Language: English
Additional information: © Author(s) (or their employer[s]) 2022. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license (http://creativecommons.org/licenses/by-nc/4.0/).
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10149206
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