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

TL;DR

Researchers developed a new type of antibody that targets CD20 on B-cell lymphoma cells and activates T cells to destroy tumors, showing strong potential for treating B-cell malignancies.

Contribution

The study introduces TFAB002s, novel non-IgG-like bispecific antibodies that target CD20 and CD3 for B-cell lymphoma treatment.

Findings

TFAB002s show strong CD20 binding and moderate CD3 binding, leading to T-cell activation and tumor cell lysis in vitro.

They demonstrate potent cytotoxicity against B-cell malignancies with varying CD20 expression levels.

In vivo experiments in a mouse model showed strong pharmacodynamic activity of TFAB002s.

Abstract

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.

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