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eIg-based bispecific T-cell engagers targeting EGFR: Format matters
Bispecific antibodies are molecules with versatile modes of action and applications for therapy. They are commonly developed as T-cell engagers (TCE), which simultaneously target an antigen expressed by tumor cells and CD3 expressed by T-cells, thereby inducing T-cell-mediated target cell killing. T...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988351/ https://www.ncbi.nlm.nih.gov/pubmed/36864566 http://dx.doi.org/10.1080/19420862.2023.2183540 |
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author | Kühl, Lennart Schäfer, Annelie K. Kraft, Sebastian Aschmoneit, Nadine Kontermann, Roland E. Seifert, Oliver |
author_facet | Kühl, Lennart Schäfer, Annelie K. Kraft, Sebastian Aschmoneit, Nadine Kontermann, Roland E. Seifert, Oliver |
author_sort | Kühl, Lennart |
collection | PubMed |
description | Bispecific antibodies are molecules with versatile modes of action and applications for therapy. They are commonly developed as T-cell engagers (TCE), which simultaneously target an antigen expressed by tumor cells and CD3 expressed by T-cells, thereby inducing T-cell-mediated target cell killing. There is growing evidence that the molecular composition and valency for the target antigen influence the activity of TCEs. Here, the eIg platform technology was used to generate a set of bispecific TCEs targeting epidermal growth factor receptors (EGFR) and CD3. These molecules either included or lacked an Fc region and exhibited one binding site for CD3 and either one or two binding sites for EGFR (1 + 1 or 2 + 1 formats) utilizing different molecular arrangements of the binding sites. In total, 11 different TCE formats were analyzed for binding to target cells and T cells, T cell-mediated killing of tumor cells, and for the activation of T cells (release of cytokines and proliferation of T-cells). Bivalent binding to EGFR strongly increased binding and T cell-mediated killing. However, the molecular composition and position of the CD3-binding arm also affected target cell killing, cytokine release, and T-cell proliferation. Our findings support that screening of a panel of formats is beneficial to identify the most potent bispecific TCE, and that format matters. |
format | Online Article Text |
id | pubmed-9988351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-99883512023-03-07 eIg-based bispecific T-cell engagers targeting EGFR: Format matters Kühl, Lennart Schäfer, Annelie K. Kraft, Sebastian Aschmoneit, Nadine Kontermann, Roland E. Seifert, Oliver MAbs Report Bispecific antibodies are molecules with versatile modes of action and applications for therapy. They are commonly developed as T-cell engagers (TCE), which simultaneously target an antigen expressed by tumor cells and CD3 expressed by T-cells, thereby inducing T-cell-mediated target cell killing. There is growing evidence that the molecular composition and valency for the target antigen influence the activity of TCEs. Here, the eIg platform technology was used to generate a set of bispecific TCEs targeting epidermal growth factor receptors (EGFR) and CD3. These molecules either included or lacked an Fc region and exhibited one binding site for CD3 and either one or two binding sites for EGFR (1 + 1 or 2 + 1 formats) utilizing different molecular arrangements of the binding sites. In total, 11 different TCE formats were analyzed for binding to target cells and T cells, T cell-mediated killing of tumor cells, and for the activation of T cells (release of cytokines and proliferation of T-cells). Bivalent binding to EGFR strongly increased binding and T cell-mediated killing. However, the molecular composition and position of the CD3-binding arm also affected target cell killing, cytokine release, and T-cell proliferation. Our findings support that screening of a panel of formats is beneficial to identify the most potent bispecific TCE, and that format matters. Taylor & Francis 2023-03-02 /pmc/articles/PMC9988351/ /pubmed/36864566 http://dx.doi.org/10.1080/19420862.2023.2183540 Text en © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Report Kühl, Lennart Schäfer, Annelie K. Kraft, Sebastian Aschmoneit, Nadine Kontermann, Roland E. Seifert, Oliver eIg-based bispecific T-cell engagers targeting EGFR: Format matters |
title | eIg-based bispecific T-cell engagers targeting EGFR: Format matters |
title_full | eIg-based bispecific T-cell engagers targeting EGFR: Format matters |
title_fullStr | eIg-based bispecific T-cell engagers targeting EGFR: Format matters |
title_full_unstemmed | eIg-based bispecific T-cell engagers targeting EGFR: Format matters |
title_short | eIg-based bispecific T-cell engagers targeting EGFR: Format matters |
title_sort | eig-based bispecific t-cell engagers targeting egfr: format matters |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988351/ https://www.ncbi.nlm.nih.gov/pubmed/36864566 http://dx.doi.org/10.1080/19420862.2023.2183540 |
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