[The mechanism of anti-tumor immune response against mouse melanoma to xenogeneic vaccination].
OBJECTIVE
To investigate the immunological mechanism for inhibiting melanoma growth in mouse by vaccination with xenogeneic melanocytes.


METHODS
Xenogeneic vaccine was prepared from pig eye melanocytes. By means of indirect ELISA the antibodies against pig melanocytes and B16 melanoma cells in immunized mice sera were detected and the immunoglobulin subclass were analyzed. Then after purification, the immunoglobulins were used for the inhibition of cell proliferation in vitro. Analyses of cross-reactive antigen in both pig melanocytes and B16 melanoma cells were performed by Western blot. Xenogeneic vaccine was used before B16 melanoma challenge in C57 BL/c mice and then the growth of tumor was monitored. Meanwhile, other mice immunized with xenogeneic vaccine were depleted of NK cells or CD4+ or CD8+ T lymphocytes.


RESULTS
The antibodies against pig melanocytes and B16 melanoma cells in mice sera were not detected by indirect ELISA until 2 weeks after first xenogeneic vaccination, and after the first finding, the antibody titers increased with the time of immunization. The anti-tumor activity and production of autoantibodies, conspicuously those of the elevated IgG, could be abrogated by the depletion of CD4+ T lymphocytes. The cross-reactive antigen with 180 kda protein in both pig melanocytes and B16 melanoma cells was confirmed. Xenogeneic vaccination resulted in inhibition of tumor growth in 90% of the immunized mice. The protective immune response elicited in this fashion was dispelled in the mice depleted of CD4+ T lymphocytes. However this response was found in 70% of the mice depleted of CD8+ T lymphocytes, and the depletion NK cells did not influence the anti-tumor effect of the vaccine.


CONCLUSIONS
The anti-tumor immune response is capable of inhibiting melanoma growth; both humoral immunity and cellular immunity could be induced by xenogeneic melanocytes vaccination. This immune response is mainly mediated by CD4+ T lymphocytes.
Luo
Feng
F
Key Lab. of Biotherapy of Human Diseases, Ministry of Education, PR China, West China Hospital, Sichuan University, Chengdu 610041, China.
Mao
Yong-qiu
YQ
Kan
Bing
B
He
Qiu-Ming
QM
Jiang
Yu
Y
Peng
Feng
F
Yang
Li
L
Tian
Ling
L
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic; D005260:Female; D008213:Lymphocyte Activation; D008297:Male; D008544:Melanocytes / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D013552:Swine; D014407:Tumor Cells, Cultured; D014611:Vaccination
D019496:Cancer Vaccines