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Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment

In the era of highly promising novel targeted-immunotherapy strategies for multiple myeloma (MM), the first series of clinical trials with CAR T-cells targeting the plasma cell-specific B-cell maturation antigen (BCMA) have shown excellent response rates. In the long-term, however, MM appears to esc...

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Autores principales: van der Schans, Jort J., van de Donk, Niels W. C. J., Mutis, Tuna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419675/
https://www.ncbi.nlm.nih.gov/pubmed/32850436
http://dx.doi.org/10.3389/fonc.2020.01362
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author van der Schans, Jort J.
van de Donk, Niels W. C. J.
Mutis, Tuna
author_facet van der Schans, Jort J.
van de Donk, Niels W. C. J.
Mutis, Tuna
author_sort van der Schans, Jort J.
collection PubMed
description In the era of highly promising novel targeted-immunotherapy strategies for multiple myeloma (MM), the first series of clinical trials with CAR T-cells targeting the plasma cell-specific B-cell maturation antigen (BCMA) have shown excellent response rates. In the long-term, however, MM appears to escape the therapy likely due to initial low and heterogeneous expression or downregulation of BCMA expression. Several other molecules targeted by CAR T-cells in MM are expressed at high levels on MM cells, but many of these attractive targets are also expressed on various, sometimes vital non-malignant cells, posing major risks for on-target, off-tumor side effects. CAR T-cell therapy for MM therefore faces two urgent challenges: (i) improving the efficacy of BCMA CAR T-cells and (ii) establishing a MM-selectivity even when CAR T-cells are directed against not entirely MM-specific target antigens. In this review, we will outline the current attempts to tackle these challenges, with a specific focus on how dual CAR targeting might be applied to tackle both issues.
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spelling pubmed-74196752020-08-25 Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment van der Schans, Jort J. van de Donk, Niels W. C. J. Mutis, Tuna Front Oncol Oncology In the era of highly promising novel targeted-immunotherapy strategies for multiple myeloma (MM), the first series of clinical trials with CAR T-cells targeting the plasma cell-specific B-cell maturation antigen (BCMA) have shown excellent response rates. In the long-term, however, MM appears to escape the therapy likely due to initial low and heterogeneous expression or downregulation of BCMA expression. Several other molecules targeted by CAR T-cells in MM are expressed at high levels on MM cells, but many of these attractive targets are also expressed on various, sometimes vital non-malignant cells, posing major risks for on-target, off-tumor side effects. CAR T-cell therapy for MM therefore faces two urgent challenges: (i) improving the efficacy of BCMA CAR T-cells and (ii) establishing a MM-selectivity even when CAR T-cells are directed against not entirely MM-specific target antigens. In this review, we will outline the current attempts to tackle these challenges, with a specific focus on how dual CAR targeting might be applied to tackle both issues. Frontiers Media S.A. 2020-08-05 /pmc/articles/PMC7419675/ /pubmed/32850436 http://dx.doi.org/10.3389/fonc.2020.01362 Text en Copyright © 2020 van der Schans, van de Donk and Mutis. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
van der Schans, Jort J.
van de Donk, Niels W. C. J.
Mutis, Tuna
Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment
title Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment
title_full Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment
title_fullStr Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment
title_full_unstemmed Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment
title_short Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment
title_sort dual targeting to overcome current challenges in multiple myeloma car t-cell treatment
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419675/
https://www.ncbi.nlm.nih.gov/pubmed/32850436
http://dx.doi.org/10.3389/fonc.2020.01362
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