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An abstract of the article "A New Strategy for Cancer Therapy: Application of Adenovirus-Mediated Complete- Length Antibody Gene," by Chen Jie, Jiang Minghong, Guo Minggao, Su Changqing, Wang Xinghua, Cui Zhenfu, Liu Xinyuan, Wu Mengchao and Qian Qijun is presented.

Therapeutic monoclonal antibody is increasingly applied in clinic with great clinical success, while its widespread application is limited by antibody manufacturing capability. Adenovirus is considered ad the one of the most proper vector for pre-clinical and clinical application, however, the application of adenoviral vector is restricted by CAR expression on the target cells. Thus adenovirus mediating anti-tumor antigen antibody expression in non-tumor cells or tumor cells is a novel strategy for cancer gene therapy. Herein we present an adenoviral delivery system that allows in vivo sufficient and sustained full-length antibody expression.Antibody heavy and light chains were expressed either separately by the two different expression cassettes or by a bi-cistronic expression vector with IRES. Using this delivery system, we generated recombinant adenoviruses encoding the anti-CD20 antibody Rituxan (Ad-RTX) or anti-Her2 antibody Trasuzumab (Ad-Tab). A single dose of Ad-RTX at 1.0×1011 VP/kg resulted in not only complete tumor elimination in Raji-inoculated nude mice but also a radical B cell depletion in the peripheral blood (0.2%) and bone marrow (0.2%) as long as 70 days after injection via tail vein in cynomolgus monkey. A single intravenous injection of 2×109 pfu of Ad5-Tab per mouse resulted in not only a sustained serum antibody level higher than 40μg/ml for at least 4 weeks in nude mice but also significant tumor elimination in 60% of experimental mice. The expressed antibody was mainly distributed in the liver and lung, as there is no antibody expression detected in other tissue in vivo. The liver toxicity induced by adenovirus and anti-adenovirus antibody produced in cynomolgus monkeys were further investigated. There is no detectable liver toxicity or anti-adenovirus neutralizing antibody in the serum in cynomolgus monkey.These observations denote that Ad-RTX or Ad-Tab may be developed into a new alternative to antibody protein therapy due to its high anti-tumor efficacy in rodent and non-human primate animals. Our study indicates that this adenovirus-mediated full-length antibody delivery system is practicable, and also can be used for the exploitation of different antibodies, without being hampered by the sophisticate protein preparation and purification processes, which can shorten the duration and reduce the expense of antibody developments. (See Figs 1 and Table).Molecular Therapy (2006) 13, S104–S104; doi: 10.1016/j.ymthe.2006.08.325 [ABSTRACT FROM AUTHOR]