RT Journal Article
SR Electronic
T1 Time to evolve: predicting engineered T cell-associated toxicity with next-generation models
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e003486
DO 10.1136/jitc-2021-003486
VO 10
IS 5
A1 Donnadieu, Emmanuel
A1 Luu, Maik
A1 Alb, Miriam
A1 Anliker, Brigitte
A1 Arcangeli, Silvia
A1 Bonini, Chiara
A1 De Angelis, Biagio
A1 Choudhary, Rashmi
A1 Espie, David
A1 Galy, Anne
A1 Holland, Cam
A1 Ivics, Zoltán
A1 Kantari-Mimoun, Chahrazade
A1 Kersten, Marie Jose
A1 Köhl, Ulrike
A1 Kuhn, Chantal
A1 Laugel, Bruno
A1 Locatelli, Franco
A1 Marchiq, Ibtissam
A1 Markman, Janet
A1 Moresco, Marta Angiola
A1 Morris, Emma
A1 Negre, Helene
A1 Quintarelli, Concetta
A1 Rade, Michael
A1 Reiche, Kristin
A1 Renner, Matthias
A1 Ruggiero, Eliana
A1 Sanges, Carmen
A1 Stauss, Hans
A1 Themeli, Maria
A1 Van den Brulle, Jan
A1 Hudecek, Michael
A1 Casucci, Monica
YR 2022
UL http://jitc.bmj.com/content/10/5/e003486.abstract
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.