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

	Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-cell deletion in mice and nonhuman primate cynomolgus monkey
	Chen, J; Su, CQ; Lu, QJ; Shi, WF; Zhang, Q; Wang, XH; Long, J; Yang, Q; Li, LF; Jia, XY
刊名	MOLECULAR CANCER THERAPEUTICS
	2008
卷号	7 期号:6 页码:1562-1568
通讯作者	Qian, QJ (reprint author), Second Mil Med Univ, Lab Viral & Gene Therapy, Eastern Hepatobiliary Surg Hosp, Shanghai 200438, Peoples R China.,qianqj@sino-gene.cn
英文摘要	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 mu g/mL at day 14, and maintained a high serum concentration of >40 mu g/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.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	NON-HODGKINS-LYMPHOMA ; ADENOASSOCIATED VIRAL VECTORS ; HUMAN MONOCLONAL-ANTIBODY ; GENE-TRANSFER ; IN-VIVO ; THERAPY ; RITUXIMAB ; IDEC-C2B8 ; CYTOTOXICITY ; EXPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000256955900023
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1395]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Chen, J,Su, CQ,Lu, QJ,et al. Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-cell deletion in mice and nonhuman primate cynomolgus monkey[J]. MOLECULAR CANCER THERAPEUTICS,2008,7(6):1562-1568.
APA	Chen, J.,Su, CQ.,Lu, QJ.,Shi, WF.,Zhang, Q.,...&Qian, QJ.(2008).Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-cell deletion in mice and nonhuman primate cynomolgus monkey.MOLECULAR CANCER THERAPEUTICS,7(6),1562-1568.
MLA	Chen, J,et al."Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-cell deletion in mice and nonhuman primate cynomolgus monkey".MOLECULAR CANCER THERAPEUTICS 7.6(2008):1562-1568.