title: 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.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Fujia
authors.initials: F
authors.lastname: Lv
authors.forename: Yuhe
authors.initials: Y
authors.lastname: Qiu
authors.forename: Yaxi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shilian
authors.initials: S
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Dexian
authors.initials: D
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins