title: Active antitumor immunity elicited by vaccine based on recombinant form of epidermal growth factor receptor.
abstract: Active immunotherapy targeting epidermal growth factor receptor (EGFR) should be another attractive approach to the treatment of EGFR-positive tumors. To test this concept, the authors evaluated the potential immune responses and antitumor activities elicited by dendritic cells pulsed with recombinant ectodomain of mouse EGFR (DC-edMER). Spleen cells isolated from DC-edMER-vaccinated mice showed a high quantity of EGFR-specific antibody-producing cells. EGFR-reactive antibody in sera isolated from vaccinated mice was identified and shown to be effective against tumors in vitro and in vivo by adoptive transfer. DC-edMER vaccine also elicited cytotoxic T-lymphocyte responses that could mediate antitumor effects in vitro and adoptive transfer in vivo. In addition, EGFR-specific cytokines responses were elicited by DC-edMER vaccine. Immunization with DC-edMER resulted in tumor regression and prolonged survival in mice challenged with Lewis lung carcinomas and mammary cancer models. Depletion of CD4+ T lymphocytes could completely abrogate the antitumor activity and EGFR-specific antibody responses, whereas the depletion of CD8+ T lymphocytes showed partial abrogation of the antitumor activity but antibody was still detected. Furthermore, tumor-induced angiogenesis was suppressed in DC-edMER-vaccinated mice or mice treated with antibody adoptive transfer. Taken together, these findings suggest the antitumor immunity could be induced by DC-edMER, which may involve both humoral and cellular immunity, and may provide insight into the treatment of EGFR-positive tumors through the induction of active immunity against EGFR.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: You
authors.initials: Y
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.forename: Jiyan
authors.initials: J
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Niu
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.forename: Qiuming
authors.initials: Q
authors.lastname: He
authors.forename: Jingmei
authors.initials: J
authors.lastname: Su
authors.forename: Meijuan
authors.initials: M
authors.lastname: Huang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Lou
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Bing
authors.initials: B
authors.lastname: Kan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000633:toxicity; D018827:Carcinoma, Lewis Lung / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D007110:Immunity, Active; D008212:Lymphocyte Depletion; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000633:toxicity
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D016207:Cytokines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D066246:ErbB Receptors