Human T lymphocyte responses against lung cancer induced by recombinant truncated mouse EGFR.
The induction of active cellular responses against EGFR should be a promising approach for the treatment of those receptor-positive tumors. However, the immunity against EGFR is presumably difficult to elicit by vaccine based on self or syngeneic EGFR due to the immune tolerance acquired during the development in immune system. We proposed a model to break immune tolerance against self-EGFR through an altered immunogen source based on xenogeneic homologous EGFR. We have previously shown human EGFR as a xenoantigen could induce specific immune responses in mouse and cross-react with mouse EGFR, and resulted in therapeutic benefits for EGFR-positive mouse tumor. Here, we show a recombinant form of extracellular domain of mouse EGFR, in the presence of DCs, could activate human peripheral T cells to proliferate, secret IFN-gamma, the induced responses could cross-react with human EGFR and kill autologous EGFR-positive lung cancer cells which could be blocked by anti-CD8 and anti-MHC class I antibody. There is no detectable cytotoxical activity against lung tissue, liver tissue and kidney tissue derived from paracancerous normal tissue. These observations suggest that antitumor immunity induced by the truncated mouse EGFR may be provoked in a cross-reaction between mouse EGFR and self-EGFR, and may provide insight into treatment of EGFR-positive tumors through induction of the autoimmune responses against EGFR.
Hu
Bing
B
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Guo Xue Xiang, No. 37, Chengdu, Sichuan, 610041, The People's Republic of China.
Wei
Yu-quan
YQ
Tian
Ling
L
Zhao
Xia
X
Lu
You
Y
Wu
Yang
Y
Yao
Bing
B
Zhang
Xiao-wei
XW
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D003429:Cross Reactions; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008175:Lung Neoplasms / Q000276:immunology*; D051379:Mice; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000276:immunology
D015478:Antigens, Heterophile; D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; D066246:ErbB Receptors