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

Donnadieu E, Luu M, Alb M, Anliker B, Arcangeli S, Bonini C, De Angelis B, Choudhary R, Espie D, Galy A, Holland C, Ivics Z, Kantari-Mimoun C, Kersten MJ, Koehl U, Kuhn C, Laugel B, Locatelli F, Marchiq I, Markman J, Moresco MA, Morris E, Negre H, Quintarelli C, Rade M, Reiche K, Renner M, Ruggiero E, Sanges C, Stauss H, Themeli M, Van Den Brulle J, Hudecek M, Casucci M (2022)

Publication Type: Journal article, Review article

Publication year: 2022

Journal

Book Volume: 10

Journal Issue: 5

DOI: 10.1136/jitc-2021-003486

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.

Involved external institutions

Universitätsklinikum Würzburg Germany (DE) Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI) Germany (DE) Università Vita-Salute San Raffaele (UniSR) Italy (IT) Università degli studi "La Sapienza" Italy (IT) Takeda Pharmaceuticals U.S.A., Inc. United States (USA) (US) Technological Research Accelerator in Genomic Therapy (ART-TG) France (FR) Universität Leipzig Germany (DE) Université de Paris France (FR) Janssen Pharmaceutica NV Belgium (BE) Fraunhofer-Institut für Zelltherapie und Immunologie (IZI) Germany (DE) Laboratoires Servier France (FR) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra Netherlands (NL) University College London (UCL) United Kingdom (GB) T-CURX GmbH Germany (DE)

How to cite

APA:

Donnadieu, E., Luu, M., Alb, M., Anliker, B., Arcangeli, S., Bonini, C.,... Casucci, M. (2022). Time to evolve: predicting engineered T cell-associated toxicity with next-generation models. Journal for ImmunoTherapy of Cancer, 10(5). https://doi.org/10.1136/jitc-2021-003486

MLA:

Donnadieu, Emmanuel, et al. "Time to evolve: predicting engineered T cell-associated toxicity with next-generation models." Journal for ImmunoTherapy of Cancer 10.5 (2022).

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