Jing Zeng1,2, Ran Liu3, Jinjing Wang3, Yi Fang4. 1. Endocrinology Department, Affiliated Hospital of the Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, People's Republic of China. zjing1125@163.com. 2. Cancer Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People's Republic of China. zjing1125@163.com. 3. Endocrinology Department, Affiliated Hospital of the Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, People's Republic of China. 4. Endocrinology Department, Affiliated Hospital of the Academy of Military Medical Sciences, 8 Dongdajie, Beijing, 100071, People's Republic of China. fangyi307@163.com.
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.
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-CD20rituximab 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.
Authors: Jamie Honeychurch; Waleed Alduaij; Mahsa Azizyan; Eleanor J Cheadle; Helene Pelicano; Andrei Ivanov; Peng Huang; Mark S Cragg; Tim M Illidge Journal: Blood Date: 2012-02-21 Impact factor: 22.113
Authors: Junji Uchida; Yasuhito Hamaguchi; Julie A Oliver; Jeffrey V Ravetch; Jonathan C Poe; Karen M Haas; Thomas F Tedder Journal: J Exp Med Date: 2004-06-21 Impact factor: 14.307