TY - JOUR
T1 - Time 2EVOLVE
T2 - predicting efficacy of engineered T-cells - how far is the bench from the bedside?
AU - Guedan, Sonia
AU - Luu, Maik
AU - Ammar, Delphine
AU - Barbao, Paula
AU - Bonini, Chiara
AU - Bousso, Philippe
AU - Buchholz, Christian J.
AU - Casucci, Monica
AU - de Angelis, Biagio
AU - Donnadieu, Emmanuel
AU - Espie, David
AU - Greco, Beatrice
AU - Groen, Richard
AU - Huppa, Johannes B.
AU - Kantari-Mimoun, Chahrazade
AU - Laugel, Bruno
AU - Mantock, Mary
AU - Markman, Janet L.
AU - Morris, Emma
AU - Quintarelli, Concetta
AU - Rade, Michael
AU - Reiche, Kristin
AU - Rodriguez-Garcia, Alba
AU - Rodriguez-Madoz, Juan Roberto
AU - Ruggiero, Eliana
AU - Themeli, Maria
AU - Hudecek, Michael
AU - Marchiq, Ibtissam
N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - 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.
AB - 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.
KW - Cell Engineering
KW - Drug Evaluation, Preclinical
KW - Immunotherapy, Adoptive
KW - Receptors, Chimeric Antigen
KW - T-Lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=85130047492&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jitc-2021-003487
DO - https://doi.org/10.1136/jitc-2021-003487
M3 - Review article
C2 - 35577501
SN - 2051-1426
VL - 10
JO - Journal for Immunotherapy of Cancer
JF - Journal for Immunotherapy of Cancer
IS - 5
ER -