[Xenogeneic melanoma-related antigen elicits anti-tumor immune response, companied by autoimmune injury].
OBJECTIVE
To investigate the relationship between anti-tumor immune response and autoimmunity elicited by adenovirus-mediated xenogeneic melanoma-related antigen tyrosinase-related protein 2 (TRP2).


METHODS
Mice divided into three groups were intradermally immunized by dl 70-3 (control group), Ad hTRP2, and Ad hTRP2 respectively. Analysis of the killing activity and production of interferon (IFN) gamma of tumor-specific cytotoxia T lymphocytes (CTL) from the C57BL/6 mice (3 mice per group) immunized with adenoviral vector encoding human or murine TRP2 (Ad hTRP2 or Ad mTRP2) were made using in vivo CTL and intracellular staining of IFN-gamma respectively. Additionally, the survival of mice (10 mice per group) immunized with Ad hTRP2 or Ad mTRP2 was checked after the subcutaneous inoculation with mouse melanoma B16.F10 cells.


RESULTS
The CTL lysis activity elicited by Ad hTRP2 was related to the duration of immunization, which increased up to peak one week after the immunization and subsequently decreased. Moreover, the Ad hTRP2-elicited CTL lysis was dose-dependent. The 6 h CTL killing and spleen IFN-gamma-producing CD8(+) T cells in total CD8(+) T cells by one week's immunization with Ad hTRP2 were 94% +/- 5% and 0.87% +/- 0.12%, respectively, whereas the 6 h CTL killing and spleen IFN-gamma-producing CD8(+) T cells by Ad mTRP2 were 22% +/- 8% and 0.15% +/- 0.05% respectively. On the other hand, 80%of the mice inoculated with 1 x 10(6) B16.F10 cells a week after the immunization with Ad hTRP2 were tumor-free for three months, but companied by formation of vitiligo in the Ad injection sites. However, only 20% of the Ad mTRP2-immunized mice inoculated with 1 x 10(5) B16.F10 cells survived, and no vitiligo was formatted.


CONCLUSIONS
Adenovirus-mediated xenogeneic melanoma-related antigen TRP2 effectively breaks immune tolerance, thus inducing strong antigen-specific cytotoxic T cell response, simultaneously companied by obvious autoimmune injury.
Tan
Xiao-hua
XH
Centre for Diagnosis and Therapy of Tumors, Beijing Army General Hospital, Beijing 100700, China. xiaohua_t@hotmail.com
Wan
Yong-hong
YH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D007114:Immunization; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011897:Random Allocation; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D050052:TRPC Cation Channels / Q000276:immunology*
D015478:Antigens, Heterophile; D000951:Antigens, Neoplasm; D050052:TRPC Cation Channels; C491859:TRPC2 protein, human; C491858:Trpc2 protein, mouse