In Vitro and In Vivo Evaluation of a Humanized Anti-APRIL Antibody

	In Vitro and In Vivo Evaluation of a Humanized Anti-APRIL Antibody
	Gao, Q.1; Li, Q.2; Xue, Z.3; Wu, P.3 ; Yang, X.3
发表期刊	CURRENT MOLECULAR MEDICINE
	2013-03-01
卷号	13 期号:3 页码:464-465
文章类型	Article
摘要	A proliferation-inducing ligand (APRIL) is overexpressed in many cancers such as colorectal, gastric and liver. Silence APRIL gene or neutralize its expression may serve as therapeutic strategies to manage those cancers. Current phase I clinical trial shows that heavily pretreated patients were well tolerated high dose intravenous infusion. Herein, we report a humanized antibody (Ab) that neutralizes APRIL protein and inhibits cancer cell proliferation both in vitro and in vivo. The Ab was generated through conjugating foreign immunodominant T-helper cell (Th) epitopes to the N- or C-terminal of four soluble APRIL mutants. In vitro anti-proliferation effects were evaluated in both Raji and Jurkat cell lines. In vivo inhibition of tumor growth was determined in a tumor xenograft animal model with green fluorescent protein (GFP) positive Raji cell line. In vitro data demonstrated that this Ab significantly inhibited both Raji and Jurkat cell proliferation in a dose-dependent manner. The molecular imaging data demonstrated in vivo tumor growth delay when animals were treated with Ab. In conclusion, we have developed a humanized anti-APRIL Ab, which is effective in inhibiting tumor cell proliferations both in vitro and vivo. The humanized Ab has potential to reduce the immunoresponse in the clinical situation. This Ab also can be used in other APRIL mediated diseases such as Sjogren syndrome, multiple sclerosis and systemic lupus erythematosus.
关键词	a Proliferation-inducing Ligand April Tumor Necrosis Factor (Tnf) Tumorigenesis
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]	CHRONIC LYMPHOCYTIC-LEUKEMIA ; BAFF ; EXPRESSION ; SURVIVAL ; BLYS
收录类别	SCI
语种	英语
项目资助者	National Natural Science Foundation of China(81171385)
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000317116100016
引用统计	被引频次：7[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/4049
专题	中国科学院分子影像重点实验室
作者单位	1.Acad Mil Med Sci, Lab Anim Ctr, Beijing 100850, Peoples R China 2.Chongqing Sci & Technol Commiss, Intellectual Property Bur, Chongqing, Peoples R China 3.Chinese Acad Sci, Inst Automat, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Gao, Q.,Li, Q.,Xue, Z.,et al. In Vitro and In Vivo Evaluation of a Humanized Anti-APRIL Antibody[J]. CURRENT MOLECULAR MEDICINE,2013,13(3):464-465.
APA	Gao, Q.,Li, Q.,Xue, Z.,Wu, P.,&Yang, X..(2013).In Vitro and In Vivo Evaluation of a Humanized Anti-APRIL Antibody.CURRENT MOLECULAR MEDICINE,13(3),464-465.
MLA	Gao, Q.,et al."In Vitro and In Vivo Evaluation of a Humanized Anti-APRIL Antibody".CURRENT MOLECULAR MEDICINE 13.3(2013):464-465.