Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-cell deletion in mice and nonhuman primate cynomolgus monkey.

Jie Chen, Changqing Su, Qiujun Lu, Wenfang Shi, Qi Zhang, Xinghua Wang, Ju Long, Qin Yang, Linfang Li, Xiaoyuan Jia, Jianming Wang, Wanming Da, Xinyuan Liu, Mengchao Wu, Qijun Qian

Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgical Hospital, The Second Military Medical University, Shanghai, People's Republic of China.

Molecular cancer therapeutics 2008 Jun

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Therapeutic monoclonal anti-CD20 antibody (Rituxan) is increasingly applied to treat B-cell-related hematologic malignancies and autoimmune disorders with great clinical success, whereas its widespread application is limited by antibody manufacturing capability. Here, we explored a quick and economical adenovirus-mediated anti-CD20 antibody generating system to directly produce anti-CD20 antibody in vivo. We generated a recombinant adenovirus encoding the anti-CD20 antibody gene and found that infection of cells with this recombinant adenovirus led to the generation of anti-CD20 antibody in cells with a similar CD20 binding affinity and specificity as commercial product Rituxan. After one single administration of the anti-CD20-expressing adenoviruses through tail vein at a dose of 1 x 10(9) plaque-forming units/mouse in nude mice, anti-CD20 antibody in the serum was detectable at day 3, reached to the peak value of 246.34 microg/mL at day 14, and maintained a high serum concentration of >40 microg/mL for 56 days. Furthermore, the in vivo generation of anti-CD20 antibody led a complete elimination of preestablished B-cell lymphoma Raji cells in nude mice, and a single administration of the anti-CD20-expressing adenovirus at a dose of 2.0 x 10(9) plaque-forming units/kg in cynomolgus monkey led a continuous B-cell deletion in circulation blood and bone marrow. These observations thus suggest that adenovirus-mediated in vivo generation of anti-CD20 antibody may serve as a new strategy to combat B-cell-related hematologic disorders.

Citation

Jie Chen, Changqing Su, Qiujun Lu, Wenfang Shi, Qi Zhang, Xinghua Wang, Ju Long, Qin Yang, Linfang Li, Xiaoyuan Jia, Jianming Wang, Wanming Da, Xinyuan Liu, Mengchao Wu, Qijun Qian. Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-cell deletion in mice and nonhuman primate cynomolgus monkey. Molecular cancer therapeutics. 2008 Jun;7(6):1562-8