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.

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, M. J., Kohl, U., Kuhn, C., Laugel, B., Locatelli, F., Marchiq, I., Markman, J., Moresco, M. A., 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., Time to evolve: predicting engineered T cell-associated toxicity with next-generation models, <<JOURNAL FOR IMMUNOTHERAPY OF CANCER>>, 2022; 10 (5): 1-18. [doi:10.1136/jitc-2021-003486] [https://hdl.handle.net/10807/229207]

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

Locatelli, Franco
Writing – Review & Editing
;
2022

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.
2022
Inglese
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, M. J., Kohl, U., Kuhn, C., Laugel, B., Locatelli, F., Marchiq, I., Markman, J., Moresco, M. A., 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., Time to evolve: predicting engineered T cell-associated toxicity with next-generation models, <<JOURNAL FOR IMMUNOTHERAPY OF CANCER>>, 2022; 10 (5): 1-18. [doi:10.1136/jitc-2021-003486] [https://hdl.handle.net/10807/229207]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/229207
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