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Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma
Multiple myeloma (MM) patients eventually develop multi-drug-resistant disease with poor survival. Hence, the development of novel treatment strategies is of great importance. Recently, different classes of immunotherapeutic agents have shown great promise in heavily pre-treated MM, including T cell...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509238/ https://www.ncbi.nlm.nih.gov/pubmed/34640611 http://dx.doi.org/10.3390/jcm10194593 |
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author | Hosny, Mashhour Verkleij, Christie P. M. van der Schans, Jort Frerichs, Kristine A. Mutis, Tuna Zweegman, Sonja van de Donk, Niels W. C. J. |
author_facet | Hosny, Mashhour Verkleij, Christie P. M. van der Schans, Jort Frerichs, Kristine A. Mutis, Tuna Zweegman, Sonja van de Donk, Niels W. C. J. |
author_sort | Hosny, Mashhour |
collection | PubMed |
description | Multiple myeloma (MM) patients eventually develop multi-drug-resistant disease with poor survival. Hence, the development of novel treatment strategies is of great importance. Recently, different classes of immunotherapeutic agents have shown great promise in heavily pre-treated MM, including T cell-redirecting bispecific antibodies (BsAbs). These BsAbs simultaneously interact with CD3 on effector T cells and a tumor-associated antigen on MM cells, resulting in redirection of T cells to MM cells. This leads to the formation of an immunologic synapse, the release of granzymes/perforins, and subsequent tumor cell lysis. Several ongoing phase 1 studies show substantial activity and a favorable toxicity profile with BCMA-, GPRC5D-, or FcRH5-targeting BsAbs in heavily pre-treated MM patients. Resistance mechanisms against BsAbs include tumor-related features, T cell characteristics, and impact of components of the immunosuppressive tumor microenvironment. Various clinical trials are currently evaluating combination therapy with a BsAb and another agent, such as a CD38-targeting antibody or an immunomodulatory drug (e.g., pomalidomide), to further improve response depth and duration. Additionally, the combination of two BsAbs, simultaneously targeting two different antigens to prevent antigen escape, is being explored in clinical studies. The evaluation of BsAbs in earlier lines of therapy, including newly diagnosed MM, is warranted, based on the efficacy of BsAbs in advanced MM. |
format | Online Article Text |
id | pubmed-8509238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85092382021-10-13 Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma Hosny, Mashhour Verkleij, Christie P. M. van der Schans, Jort Frerichs, Kristine A. Mutis, Tuna Zweegman, Sonja van de Donk, Niels W. C. J. J Clin Med Review Multiple myeloma (MM) patients eventually develop multi-drug-resistant disease with poor survival. Hence, the development of novel treatment strategies is of great importance. Recently, different classes of immunotherapeutic agents have shown great promise in heavily pre-treated MM, including T cell-redirecting bispecific antibodies (BsAbs). These BsAbs simultaneously interact with CD3 on effector T cells and a tumor-associated antigen on MM cells, resulting in redirection of T cells to MM cells. This leads to the formation of an immunologic synapse, the release of granzymes/perforins, and subsequent tumor cell lysis. Several ongoing phase 1 studies show substantial activity and a favorable toxicity profile with BCMA-, GPRC5D-, or FcRH5-targeting BsAbs in heavily pre-treated MM patients. Resistance mechanisms against BsAbs include tumor-related features, T cell characteristics, and impact of components of the immunosuppressive tumor microenvironment. Various clinical trials are currently evaluating combination therapy with a BsAb and another agent, such as a CD38-targeting antibody or an immunomodulatory drug (e.g., pomalidomide), to further improve response depth and duration. Additionally, the combination of two BsAbs, simultaneously targeting two different antigens to prevent antigen escape, is being explored in clinical studies. The evaluation of BsAbs in earlier lines of therapy, including newly diagnosed MM, is warranted, based on the efficacy of BsAbs in advanced MM. MDPI 2021-10-06 /pmc/articles/PMC8509238/ /pubmed/34640611 http://dx.doi.org/10.3390/jcm10194593 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Hosny, Mashhour Verkleij, Christie P. M. van der Schans, Jort Frerichs, Kristine A. Mutis, Tuna Zweegman, Sonja van de Donk, Niels W. C. J. Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma |
title | Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma |
title_full | Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma |
title_fullStr | Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma |
title_full_unstemmed | Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma |
title_short | Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma |
title_sort | current state of the art and prospects of t cell-redirecting bispecific antibodies in multiple myeloma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509238/ https://www.ncbi.nlm.nih.gov/pubmed/34640611 http://dx.doi.org/10.3390/jcm10194593 |
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