title: Cancer gene therapy of adenovirus-mediated anti-4-1BB scFv  in immunocompetent mice.
abstract: The use of immunostimulatory molecule genes aiming at enhancing anti-tumor immunity has emerged as a new approach to treat cancers. 4-1BB signaling, an important costimulatory pathway delivering a signal for T cell activation, survival and growth, has become one of the most promising targets for cancer immunotherapy. In this work, a recombinant nonreplicative adenovirus (Ad.4-1BB scFv) carrying a single-chain Fv fragments (scFv) specific for 4-1BB gene (anti-4-1BB scFv) was generated, haracterized and explored for its stimulation of anti-tumor immunity in immunocompetent C57BL/6 mice. Ad.4-1BB scFv could efficiently infect murine hepatoma Hepa 1-6 cells and induce anti-4-1BB scFv expression on the cell surface. Moreover, Ad.4-1BB scFv did not cause obvious cytotoxicity effect on human and murine tumor cell lines (A549, PLC/PRF/5, Hepa 1-6 and TC-1) even at a high MOI, which suggested Ad.4-1BB scFv had no direct effect on tumor cells. Intratumoral injection of Ad.4-1BB scFv to established Hepa 1-6 tumors significantly suppressed the tumor growth in C57BL/6 mice. The anti-tumor effect might be mainly attributed to the anti-4-1BB scFv-mediated immune activity, as evidenced by enhanced interferon-gamma-producing splenic cells and increased lymphocytes infiltration in the tumor microenvironment. These results indicated that nonreplicative adenovirus carrying the anti-4-1BB scFv gene possessed powerful in vivo anti-tumor efficacy and might be a valuable tool for cancer immunotherapy.
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.forename: Xun
authors.initials: X
authors.lastname: Ye
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.forename: Andre
authors.initials: A
authors.lastname: Lieber
authors.forename: Hong-Zhuan
authors.initials: HZ
authors.lastname: Chen
mesh_terms: D053330:4-1BB Ligand / Q000037:antagonists & inhibitors*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015316:Genetic Therapy; D007121:Immunocompetence / Q000502:physiology*; D007128:Immunoglobulin Fragments / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*
chemical_list: D053330:4-1BB Ligand; D007128:Immunoglobulin Fragments; C055966:immunoglobulin Fv