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

作者：Zeng, Jing; Liu, Ran; Wang, Jinjing; Fang, Yi^*

来源：Journal of Cancer Research and Clinical Oncology, 2015, 141(11): 1899-1907.

DOI：10.1007/s00432-015-1949-7

• Bispecific antibody
• Cell death
• CD20
• HLA-DR
• Lymphoma

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.
The gene for bispecific antibody CD20-HLA-DR DVD-Ig was constructed and expressed in FreeStyle (TM) 293-F cells, followed by purification. Their functions were characterized for binding to CD20 and HLA-DR and for cytotoxicity against B-cell lymphoma.
The bispecific antibody CD20-HLA-DR DVD-Ig was engineered using the DNA fragments for the anti-CD20 rituximab and anti-HLA-DR hL243 gamma 1. 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.
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.

• 出版日期2015-11
• 单位中国人民解放军总医院; 中国人民解放军军事医学科学院