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Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies

Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumom...

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Autores principales: Tapia-Galisteo, Antonio, Álvarez-Vallina, Luis, Sanz, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373336/
https://www.ncbi.nlm.nih.gov/pubmed/37501154
http://dx.doi.org/10.1186/s13045-023-01482-w
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author Tapia-Galisteo, Antonio
Álvarez-Vallina, Luis
Sanz, Laura
author_facet Tapia-Galisteo, Antonio
Álvarez-Vallina, Luis
Sanz, Laura
author_sort Tapia-Galisteo, Antonio
collection PubMed
description Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumomab) was approved by the FDA in 2014, but no other one hit the market until 2022. Now the field is gaining momentum, with three approvals in 2022 and 2023 (as of May): the anti-CD20 × anti-CD3 mosunetuzumab and epcoritamab and the anti-B cell maturation antigen (BCMA) × anti-CD3 teclistamab, and another three molecules in regulatory review. T cell engagers will likely revolutionize the treatment of hematological malignancies in the short term, as they are considerably more potent than conventional monoclonal antibodies recognizing the same tumor antigens. The field is thriving, with a plethora of different formats and targets, and around 100 bispecific T cell engagers more are already in clinical trials. Bispecific NK cell engagers are also in early-stage clinical studies and may offer similar efficacy with milder side effects. Trispecific antibodies (engaging either T cell or NK cell receptors) raise the game even further with a third binding moiety, which allows either the targeting of an additional tumor-associated antigen to increase specificity and avoid immune escape or the targeting of additional costimulatory receptors on the immune cell to improve its effector functions. Altogether, these engineered molecules may change the paradigm of treatment for relapsed or refractory hematological malignancies.
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spelling pubmed-103733362023-07-28 Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies Tapia-Galisteo, Antonio Álvarez-Vallina, Luis Sanz, Laura J Hematol Oncol Review Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumomab) was approved by the FDA in 2014, but no other one hit the market until 2022. Now the field is gaining momentum, with three approvals in 2022 and 2023 (as of May): the anti-CD20 × anti-CD3 mosunetuzumab and epcoritamab and the anti-B cell maturation antigen (BCMA) × anti-CD3 teclistamab, and another three molecules in regulatory review. T cell engagers will likely revolutionize the treatment of hematological malignancies in the short term, as they are considerably more potent than conventional monoclonal antibodies recognizing the same tumor antigens. The field is thriving, with a plethora of different formats and targets, and around 100 bispecific T cell engagers more are already in clinical trials. Bispecific NK cell engagers are also in early-stage clinical studies and may offer similar efficacy with milder side effects. Trispecific antibodies (engaging either T cell or NK cell receptors) raise the game even further with a third binding moiety, which allows either the targeting of an additional tumor-associated antigen to increase specificity and avoid immune escape or the targeting of additional costimulatory receptors on the immune cell to improve its effector functions. Altogether, these engineered molecules may change the paradigm of treatment for relapsed or refractory hematological malignancies. BioMed Central 2023-07-27 /pmc/articles/PMC10373336/ /pubmed/37501154 http://dx.doi.org/10.1186/s13045-023-01482-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Tapia-Galisteo, Antonio
Álvarez-Vallina, Luis
Sanz, Laura
Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
title Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
title_full Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
title_fullStr Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
title_full_unstemmed Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
title_short Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
title_sort bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373336/
https://www.ncbi.nlm.nih.gov/pubmed/37501154
http://dx.doi.org/10.1186/s13045-023-01482-w
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