TFAB002s, novel CD20-targeting T cell-dependent bispecific Fab-FabCH3 antibodies, exhibit potent antitumor efficacy against malignant B-cell lymphoma.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Antibodies, Bispecific*/pharmacology ; Antibodies, Bispecific*/immunology ; Antigens, CD20*/immunology ; Lymphoma, B-Cell*/immunology ; Lymphoma, B-Cell*/therapy ; Lymphoma, B-Cell*/drug therapy ; Immunoglobulin Fab Fragments*/immunology ; T-Lymphocytes*/immunology; Animals ; Mice ; Humans ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Lymphocyte Activation/immunology ; Lymphocyte Activation/drug effects ; Female

B-cell lymphoma, clinically, comprises a heterogeneous group of malignancies that encompass various subtypes. CD20 is an optimal target for therapeutic antibodies in B-cell lymphoma immunotherapy since approximately 90% of B-cell malignancies typically exhibit CD20 expression on their surface, while its presence is limited in normal tissues. In this study, we have developed a series of novel non-IgG-like T cell-dependent bispecific antibodies by constructing Fab-FabCH3, referred to as Tandem Antigen-binding Fragment 002 (TFAB002), which specifically target CD20 for the treatment of malignant B-cell lymphoma. TFAB002s display strong binding affinity with CD20 and moderate binding affinity with CD3, thereby triggering target-specific T-cell activation, cytokine release, and tumor cell lysis in vitro. Furthermore, TFAB002s exhibit potent cytotoxicity against B-cell malignancies that express varying levels of CD20. Besides, the TFAB002s show potent pharmacodynamic activity in vivo in the WIL2-S cells CDX mouse model. Collectively, these results underscore the potential of TFAB002s as a highly promising therapeutic approach for selectively depleting CD20-positive B cells, thereby warranting further clinical evaluation as a viable treatment option for CD20-expressing B-cell malignancies.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Antibodies, Bispecific)
0 (Antigens, CD20)
0 (Immunoglobulin Fab Fragments)

Date Created: 20240925 Date Completed: 20240925 Latest Revision: 20240927

20240927

PMC11423992

10.1371/journal.pone.0310889

39321199