PT  - JOURNAL ARTICLE
AU  - Donnadieu, Emmanuel
AU  - Luu, Maik
AU  - Alb, Miriam
AU  - Anliker, Brigitte
AU  - Arcangeli, Silvia
AU  - Bonini, Chiara
AU  - De Angelis, Biagio
AU  - Choudhary, Rashmi
AU  - Espie, David
AU  - Galy, Anne
AU  - Holland, Cam
AU  - Ivics, Zoltán
AU  - Kantari-Mimoun, Chahrazade
AU  - Kersten, Marie Jose
AU  - Köhl, Ulrike
AU  - Kuhn, Chantal
AU  - Laugel, Bruno
AU  - Locatelli, Franco
AU  - Marchiq, Ibtissam
AU  - Markman, Janet
AU  - Moresco, Marta Angiola
AU  - Morris, Emma
AU  - Negre, Helene
AU  - Quintarelli, Concetta
AU  - Rade, Michael
AU  - Reiche, Kristin
AU  - Renner, Matthias
AU  - Ruggiero, Eliana
AU  - Sanges, Carmen
AU  - Stauss, Hans
AU  - Themeli, Maria
AU  - Van den Brulle, Jan
AU  - Hudecek, Michael
AU  - Casucci, Monica
TI  - Time to evolve: predicting engineered T cell-associated toxicity with next-generation models
AID  - 10.1136/jitc-2021-003486
DP  - 2022 May 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e003486
VI  - 10
IP  - 5
4099  - http://jitc.bmj.com/content/10/5/e003486.short
4100  - http://jitc.bmj.com/content/10/5/e003486.full
SO  - J Immunother Cancer2022 May 01; 10
AB  - 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.