The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice
Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role o...
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Format: | Article |
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Frontiers Media S.A.
2020-05-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00888/full |
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doaj-69eebbaf67934dfbb8ff1101f08ddda1 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marco Cerrano Marco Cerrano Marco Ruella Miguel-Angel Perales Candida Vitale Candida Vitale Danilo Giuseppe Faraci Danilo Giuseppe Faraci Luisa Giaccone Luisa Giaccone Marta Coscia Marta Coscia Molly Maloy Miriam Sanchez-Escamilla Miriam Sanchez-Escamilla Hesham Elsabah Afraa Fadul Enrico Maffini Gianfranco Pittari Benedetto Bruno Benedetto Bruno |
spellingShingle |
Marco Cerrano Marco Cerrano Marco Ruella Miguel-Angel Perales Candida Vitale Candida Vitale Danilo Giuseppe Faraci Danilo Giuseppe Faraci Luisa Giaccone Luisa Giaccone Marta Coscia Marta Coscia Molly Maloy Miriam Sanchez-Escamilla Miriam Sanchez-Escamilla Hesham Elsabah Afraa Fadul Enrico Maffini Gianfranco Pittari Benedetto Bruno Benedetto Bruno The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice Frontiers in Immunology CAR T cells adoptive immunotherapy cellular therapy lymphoma leukemia |
author_facet |
Marco Cerrano Marco Cerrano Marco Ruella Miguel-Angel Perales Candida Vitale Candida Vitale Danilo Giuseppe Faraci Danilo Giuseppe Faraci Luisa Giaccone Luisa Giaccone Marta Coscia Marta Coscia Molly Maloy Miriam Sanchez-Escamilla Miriam Sanchez-Escamilla Hesham Elsabah Afraa Fadul Enrico Maffini Gianfranco Pittari Benedetto Bruno Benedetto Bruno |
author_sort |
Marco Cerrano |
title |
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice |
title_short |
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice |
title_full |
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice |
title_fullStr |
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice |
title_full_unstemmed |
The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice |
title_sort |
advent of car t-cell therapy for lymphoproliferative neoplasms: integrating research into clinical practice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-05-01 |
description |
Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role of CAR T cells in the treatment of B-cell disorders, however, is rapidly evolving. Ongoing clinical trials aim at comparing CAR T cells with standard treatment options and at evaluating their efficacy earlier in the disease course. The use of CAR T cells is still limited by the risk of relevant toxicities, most commonly cytokine release syndrome and neurotoxicity, whose management has nonetheless significantly improved. Some patients do not respond or relapse after treatment, either because of poor CAR T-cell expansion, lack of anti-tumor effects or after the loss of the target antigen on tumor cells. Investigators are trying to overcome these hurdles in many ways: by testing constructs which target different and/or multiple antigens or by improving CAR T-cell structure with additional functions and synergistic molecules. Alternative cell sources including allogeneic products (off-the-shelf CAR T cells), NK cells, and T cells obtained from induced pluripotent stem cells are also considered. Several trials are exploring the curative potential of CAR T cells in other malignancies, and recent data on multiple myeloma and chronic lymphocytic leukemia are encouraging. Given the likely expansion of CAR T-cell indications and their wider availability over time, more and more highly specialized clinical centers, with dedicated clinical units, will be required. Overall, the costs of these cell therapies will also play a role in the sustainability of many health care systems. This review will focus on the major clinical trials of CAR T cells in B-cell malignancies, including those leading to the first FDA approvals, and on the new settings in which these constructs are being tested. Besides, the most promising approaches to improve CAR T-cell efficacy and early data on alternative cell sources will be reviewed. Finally, we will discuss the challenges and the opportunities that are emerging with the advent of CAR T cells into clinical routine. |
topic |
CAR T cells adoptive immunotherapy cellular therapy lymphoma leukemia |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00888/full |
work_keys_str_mv |
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doaj-69eebbaf67934dfbb8ff1101f08ddda12020-11-25T02:59:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00888536681The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical PracticeMarco Cerrano0Marco Cerrano1Marco Ruella2Miguel-Angel Perales3Candida Vitale4Candida Vitale5Danilo Giuseppe Faraci6Danilo Giuseppe Faraci7Luisa Giaccone8Luisa Giaccone9Marta Coscia10Marta Coscia11Molly Maloy12Miriam Sanchez-Escamilla13Miriam Sanchez-Escamilla14Hesham Elsabah15Afraa Fadul16Enrico Maffini17Gianfranco Pittari18Benedetto Bruno19Benedetto Bruno20Department of Oncology/Hematology, A.O.U. Città della Salute e della Scienza di Torino, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyDepartment of Pathology and Laboratory Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United StatesAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United StatesDepartment of Oncology/Hematology, A.O.U. Città della Salute e della Scienza di Torino, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyDepartment of Oncology/Hematology, A.O.U. Città della Salute e della Scienza di Torino, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyDepartment of Oncology/Hematology, A.O.U. Città della Salute e della Scienza di Torino, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyDepartment of Oncology/Hematology, A.O.U. Città della Salute e della Scienza di Torino, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United StatesAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United StatesDepartment of Hematological Malignancies and Stem Cell Transplantation, Research Institute of Marques de Valdecilla (IDIVAL), Santander, SpainDepartment of Medical Oncology, Hematology/BMT Service, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, QatarDepartment of Medical Oncology, Hematology/BMT Service, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, QatarHematology and Stem Cell Transplant Unit, Romagna Transplant Network, Ravenna, ItalyDepartment of Medical Oncology, Hematology/BMT Service, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, QatarDepartment of Oncology/Hematology, A.O.U. Città della Salute e della Scienza di Torino, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, Turin, ItalyResearch on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role of CAR T cells in the treatment of B-cell disorders, however, is rapidly evolving. Ongoing clinical trials aim at comparing CAR T cells with standard treatment options and at evaluating their efficacy earlier in the disease course. The use of CAR T cells is still limited by the risk of relevant toxicities, most commonly cytokine release syndrome and neurotoxicity, whose management has nonetheless significantly improved. Some patients do not respond or relapse after treatment, either because of poor CAR T-cell expansion, lack of anti-tumor effects or after the loss of the target antigen on tumor cells. Investigators are trying to overcome these hurdles in many ways: by testing constructs which target different and/or multiple antigens or by improving CAR T-cell structure with additional functions and synergistic molecules. Alternative cell sources including allogeneic products (off-the-shelf CAR T cells), NK cells, and T cells obtained from induced pluripotent stem cells are also considered. Several trials are exploring the curative potential of CAR T cells in other malignancies, and recent data on multiple myeloma and chronic lymphocytic leukemia are encouraging. Given the likely expansion of CAR T-cell indications and their wider availability over time, more and more highly specialized clinical centers, with dedicated clinical units, will be required. Overall, the costs of these cell therapies will also play a role in the sustainability of many health care systems. This review will focus on the major clinical trials of CAR T cells in B-cell malignancies, including those leading to the first FDA approvals, and on the new settings in which these constructs are being tested. Besides, the most promising approaches to improve CAR T-cell efficacy and early data on alternative cell sources will be reviewed. Finally, we will discuss the challenges and the opportunities that are emerging with the advent of CAR T cells into clinical routine.https://www.frontiersin.org/article/10.3389/fimmu.2020.00888/fullCAR T cellsadoptive immunotherapycellular therapylymphomaleukemia |