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Time 2EVOLVE: predicting efficacy of engineered T-cells - how far is the bench from the bedside?

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Item Type:Review
Title:Time 2EVOLVE: predicting efficacy of engineered T-cells - how far is the bench from the bedside?
Creators Name:Guedan, S., Luu, M., Ammar, D., Barbao, P., Bonini, C., Bousso, P., Buchholz, C.J., Casucci, M., De Angelis, B., Donnadieu, E., Espie, D., Greco, B., Groen, R., Huppa, J.B., Kantari-Mimoun, C., Laugel, B., Mantock, M., Markman, J.L., Morris, E., Quintarelli, C., Rade, M., Reiche, K., Rodriguez-Garcia, A., Rodriguez-Madoz, J.R., Ruggiero, E., Themeli, M., Hudecek, M. and Marchiq, I.
Abstract:Immunotherapy with gene engineered CAR and TCR transgenic T-cells is a transformative treatment in cancer medicine. There is a rich pipeline with target antigens and sophisticated technologies that will enable establishing this novel treatment not only in rare hematological malignancies, but also in common solid tumors. The T2EVOLVE consortium is a public private partnership directed at accelerating the preclinical development of and increasing access to engineered T-cell immunotherapies for cancer patients. A key ambition in T2EVOLVE is to assess the currently available preclinical models for evaluating safety and efficacy of engineered T cell therapy and developing new models and test parameters 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. Here, we review existing and emerging preclinical models that permit assessing CAR and TCR signaling and antigen binding, the access and function of engineered T-cells to primary and metastatic tumor ligands, as well as the impact of endogenous factors such as the host immune system and microbiome. Collectively, this review article presents a perspective on an accelerated translational development path that is based on innovative standardized preclinical test systems for CAR and TCR transgenic T-cell products.
Keywords:Immunotherapy, Adoptive Immunotherapy, Neoplasms, Chimeric Antigen Receptors, T-Lymphocytes
Source:Journal for ImmunoTherapy of Cancer
ISSN:2051-1426
Publisher:BMJ Publishing Group
Volume:10
Number:5
Page Range:e003487
Date:May 2022
Official Publication:https://doi.org/10.1136/jitc-2021-003487
PubMed:View item in PubMed

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