Active antitumor immunity elicited by vaccine based on recombinant form of epidermal growth factor receptor.
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.
Hu
Bing
B
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, China.
Wei
Yuquan
Y
Tian
Ling
L
Zhao
Xia
X
Lu
You
Y
Wu
Yang
Y
Yao
Bing
B
Liu
Jiyan
J
Niu
Ting
T
Wen
Yanjun
Y
He
Qiuming
Q
Su
Jingmei
J
Huang
Meijuan
M
Lou
Yanyan
Y
Luo
Yan
Y
Kan
Bing
B
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
D000906:Antibodies; D019496:Cancer Vaccines; D016207:Cytokines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D066246:ErbB Receptors