Anti-tumor immunity elicited by adenovirus encoding AdhTrp2 or AdmTrp2 without vitiligo.
To compare the difference in tumor immunity and autoimmunity elicited by adenovirus (Ad) encoding human or murine tyrosinase-related protein 2 (AdhTRP2 or AdmTRP2), and to find the most effective way to induce immunity by AdhTRP2 or AdmTRP2, C57BL/6 mice were immunized with AdhTRP2 or AdmTRP2 intramuscularly at different doses of 10(5), 10(6), 10(7) and 10(8) separately (10 mice for each dose). Two weeks after the immunization, in vivo CTL assay and intracellular staining (ICS) of IFN-gamma were carried out to analyze the dose-effect relationship. Tumor growth and vitiligo (as an sign of autoimmunity) were observed until 3 months after challenge with 10(5) B16F10 tumor cells. The results showed that Ad encoding AdmTrp2 induced weak tumor immune response. Similar immunization with AdhTrp-2 elicited stronger protective immunity. CTL activity and IFN-gamma-produced CD8+T cells were directly proportional to dose of AdhTrp2 or AdmTrp2. Moreover, AdhTrp2 group showed tumor rejection in 100% of challenged mice till the end of 3rd month while 60% of mice immunized with AdmTrp2 were protected against tumor. In the whole process of this experiment, no vitiligo was observed in mice immunized either with AdhTrp2 or AdmTrp2. It is concluded that anti-melanoma responses induced by genetic vaccination expressing xenoantigens breaks immune tolerance effectively and is able to elicit strong antigen-specific cytotoxic T cell response without vitiligo.
Liu
Hongju
H
Department of Respiratory Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liuhj69@yahoo.com.cn
Xiong
Xianzhi
X
Li
Zuoya
Z
Xin
Jianbao
J
Tao
Xiaonan
X
Hu
Yu
Y
D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014820:Vitiligo / Q000378:metabolism*
D000970:Antineoplastic Agents; D016207:Cytokines; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase