Surmounting the obstacles that impede effective CAR T cell trafficking to solid tumors

Autor: Loïc Dupré, Emmanuel Donnadieu, Vinicius Cotta-de-Almeida, Lia Gonçalves Pinho
Přispěvatelé: Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This work was funded by Brazilian National Council for Scientific and Technological Development (CNPq), L.G.P. was supported by grant no. 140718/2019-2 and V.C.A. was supported by grant no. 310329/2019-1. The Coordination for the Improvement of Higher Education Personnel (CAPES), with support from the Program PrInt-Fiocruz-CAPES, the Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), and Mercosur Fund for Structural Convergence (FOCEM, 03/11) provided funding for L.G.P. and V.C.A. E.D. was supported by a funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 667980., European Project: 667980,H2020,H2020-PHC-2015-two-stage,CARAT(2016), PINIER, CHRISTINE, Chimeric Antigen Receptors (CARs) for Advanced Therapies - CARAT - - H20202016-01-01 - 2019-12-31 - 667980 - VALID, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Rok vydání: 2020
Předmět:
0301 basic medicine
MESH: T-Lymphocytes* / pathology
medicine.medical_treatment
T-Lymphocytes
MESH: Antigens
Neoplasm / immunology
MESH: Cell Movement / immunology
Review
Immunotherapy
Adoptive
0302 clinical medicine
Cancer immunotherapy
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Cell Movement
Neoplasms
Tumor Microenvironment
Immunology and Allergy
Cytotoxic T cell
chimeric antigen receptor engineering
Receptors
Chimeric Antigen
MESH: Neoplasms* / therapy
medicine.anatomical_structure
motility
MESH: Immunotherapy
Adoptive
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Antibody
MESH: T-Lymphocytes* / immunology
T cell
extracellular matrix
Immunology
Reviews
Biology
MESH: Neoplasms* / pathology
T cell trafficking
Guest Editors: João P.B. Viola
Lis Antonelli
Martin Bonamino
Jose Alves Filho
and Helder Nakaya
03 medical and health sciences
Antigens
Neoplasm
medicine
Humans
MESH: Receptors
Chimeric Antigen / immunology
MESH: Tumor Microenvironment / immunology
Tumor microenvironment
MESH: Humans
cancer immunotherapy
Cell Biology
Immune checkpoint
Chimeric antigen receptor
030104 developmental biology
Cancer cell
Cancer research
biology.protein
XLIV Congress of the Brazilian Society of Immunology
MESH: Neoplasms* / immunology
030215 immunology
Zdroj: Journal of Leukocyte Biology
Journal of Leukocyte Biology, 2020, 108 (4), pp.1067-1079. ⟨10.1002/JLB.1MR0520-746R⟩
ISSN: 1938-3673
0741-5400
DOI: 10.1002/JLB.1MR0520-746R⟩
Popis: Innovative immunotherapies based on immune checkpoint targeting antibodies and engineered T cells are transforming the way we approach cancer treatment. However, although these T cell centered strategies result in marked and durable responses in patients across many different tumor types, they provide therapeutic efficacy only in a proportion of patients. A major challenge of immuno‐oncology is thereby to identify mechanisms responsible for resistance to cancer immunotherapy in order to overcome them via adapted strategies that will ultimately improve intrinsic efficacy and response rates. Here, we focus on the barriers that restrain the trafficking of chimeric antigen receptor (CAR)‐expressing T cells to solid tumors. Upon infusion, CAR T cells need to home into malignant sites, navigate within complex tumor environments, form productive interactions with cancer cells, deliver their cytotoxic activities, and finally persist. We review the accumulating evidence that the microenvironment of solid tumors contains multiple obstacles that hinder CAR T cells in the dynamic steps underlying their trafficking. We focus on how these hurdles may in part account for the failure of CAR T cell clinical trials in human carcinomas. Given the engineered nature of CAR T cells and possibilities to modify the tumor environment, there are ample opportunities to augment CAR T cell ability to efficiently find and combat tumors. We present some of these strategies, which represent a dynamic field of research with high potential for clinical applicability.
Graphical Abstract Examines the barriers that restrain the trafficking of chimeric antigen receptor (CAR)‐expressing T cells to solid tumors and potential strategies to overcome these hurdles.
Databáze: OpenAIRE
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