Conditional activation of an anti-IgM antibody-drug conjugate for precise B cell lymphoma targeting
Copyright © 2023 Schoenfeld, Harwardt, Habermann, Elter and Kolmar..
Cancerous B cells are almost indistinguishable from their non-malignant counterparts regarding their surface antigen expression. Accordingly, the challenge to be faced consists in elimination of the malignant B cell population while maintaining a functional adaptive immune system. Here, we present an IgM-specific antibody-drug conjugate masked by fusion of the epitope-bearing IgM constant domain. Antibody masking impaired interaction with soluble pentameric as well as cell surface-expressed IgM molecules rendering the antibody cytotoxically inactive. Binding capacity of the anti-IgM antibody drug conjugate was restored upon conditional protease-mediated demasking which consequently enabled target-dependent antibody internalization and subsequent induction of apoptosis in malignant B cells. This easily adaptable approach potentially provides a novel mechanism of clonal B cell lymphoma eradication to the arsenal available for non-Hodgkin's lymphoma treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 29., Seite 1258700 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schoenfeld, Katrin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 23.10.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.1258700 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363340734 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Schoenfeld, Harwardt, Habermann, Elter and Kolmar. | ||
| 520 | |a Cancerous B cells are almost indistinguishable from their non-malignant counterparts regarding their surface antigen expression. Accordingly, the challenge to be faced consists in elimination of the malignant B cell population while maintaining a functional adaptive immune system. Here, we present an IgM-specific antibody-drug conjugate masked by fusion of the epitope-bearing IgM constant domain. Antibody masking impaired interaction with soluble pentameric as well as cell surface-expressed IgM molecules rendering the antibody cytotoxically inactive. Binding capacity of the anti-IgM antibody drug conjugate was restored upon conditional protease-mediated demasking which consequently enabled target-dependent antibody internalization and subsequent induction of apoptosis in malignant B cells. This easily adaptable approach potentially provides a novel mechanism of clonal B cell lymphoma eradication to the arsenal available for non-Hodgkin's lymphoma treatment | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Harwardt, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Habermann, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Elter, Adrian |e verfasserin |4 aut | |
| 700 | 1 | |a Kolmar, Harald |e verfasserin |4 aut | |
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