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Journal of Cancer Research and Clinical Oncology

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01.11.2015 | Original Article – Cancer Research

A bispecific antibody directly induces lymphoma cell death by simultaneously targeting CD20 and HLA-DR

verfasst von: Jing Zeng, Ran Liu, Jinjing Wang, Yi Fang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 11/2015

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Abstract

Purpose

Both CD20 and HLA-DR antigens are highly expressed on a variety of B-cell lymphomas and are therapeutic targets in antibody-based lymphoma therapy. The aim of this study was to evaluate the anti-tumor effect of a bispecific antibody CD20-HLA-DR DVD-Ig on B-cell lymphoma.

Methods

The gene for bispecific antibody CD20-HLA-DR DVD-Ig was constructed and expressed in FreeStyle™293-F cells, followed by purification. Their functions were characterized for binding to CD20 and HLA-DR and for cytotoxicity against B-cell lymphoma.

Results

The bispecific antibody CD20-HLA-DR DVD-Ig was engineered using the DNA fragments for the anti-CD20 rituximab and anti-HLA-DR hL243γ1. The CD20-HLA-DR DVD-Ig bound simultaneously to both CD20 and HLA-DR, induced potent complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against B-cell lymphoma, and elicited homotypic adhesion and actin reorganization. Treatment of a mixture of human whole blood and Raji cells with CD20-HLA-DR DVD-Ig effectively depleted Raji cells and had a little toxicity against normal B cells.

Conclusion

Our data indicated that targeting both CD20 and HLA-DR was an effective way against NHL, suggesting that CD20-HLA-DR DVD-Ig may be a promising therapeutic agent for B-cell lymphoma.

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Titel: A bispecific antibody directly induces lymphoma cell death by simultaneously targeting CD20 and HLA-DR
verfasst von: Jing Zeng
Ran Liu
Jinjing Wang
Yi Fang
Publikationsdatum: 01.11.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 11/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-015-1949-7

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