Adeno-associated virus-mediated anti-DR5 chimeric antibody expression suppresses human tumor growth in nude mice.

Abstract

In the present study we demonstrate that adeno-associated virus (AAV)-mediated anti-DR5 (death receptor 5) mouse-human chimeric antibody (shorten as Adximab) expression significantly suppressed tumor cell growth by inducing apoptosis both in vitro and in vivo. The viral-expressed and cell-secreted Adximab efficiently bound DR5 with an affinity of 0.7nM and induced apoptosis of various tumor cells, but not normal cells. A single intramuscular injection of recombinant AAV particles resulted in a stable expression of Adximab in mouse serum for at least 70days. AAV-mediated Adximab expression led to a significant suppression of tumor growth in nude mice receiving xenografts of human liver and colon cancer. These data suggest that chimeric antibody gene transfer may provide an alternative strategy for the therapy of varieties of cancers.

• Authors: Fujia Lv, Yuhe Qiu, Yaxi Zhang, Shilian Liu, Juan Shi, Yanxin Liu, Dexian Zheng
• Journal: Cancer letters (Cancer Lett) Vol. 302 Issue 2 Pg. 119-27 (Mar 28 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21306822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Recombinant Proteins

Topics

• Animals
• Antibodies, Monoclonal (metabolism, therapeutic use)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line, Tumor
• Dependovirus (genetics)
• Gene Expression Regulation
• Genetic Therapy (methods)
• Humans
• Immunotherapy
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms (immunology, therapy)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (genetics, therapeutic use)
• Recombinant Proteins (genetics)