[Ad hTRP2 - mediated immunity against melanoma is enhanced by dendritic cells pulsed with peptide].
OBJECTIVE
To investigate the enhanced effect of bone marrow-derived dendritic cells (DC) pulsed with SVYDFFVWL, a MHC class I peptide located in 180-188 amino acid residues of human melanoma-associated antigen tyrosinase- related protein 2 ( hTRP2) on the immunity against melanomas elicited by adenovirus encoding hTRP2 (Ad hTRP2).


METHODS
The mice were intradermally immunized with Ad hTRP2, and three weeks later with Ad hTRP2 or DC/SVYDFFVWL once more. Analysis of CTL killing activity and IFN-gamma-producing CD8 + T cells in the total CD8 + T cells of spleen were made using in vivo CTL and intracellular staining of IFN-gamma, respectively. Additionally, the survival of mice was checked after the subcutaneous inoculation with mouse melanoma B16. F10 cells.


RESULTS
The 6 h CTL killing and IFN-gamma producing CD8 +T cells in the total CD8 ' T cells of spleens were 68. 40%+/-5. 50% and 0. 67%+/-0.16% in Ad hTRP2 (priming)-Ad hTRP2 (boosting) group,28. 50%+/-6.40% and 0.22%+/-0.07% in DC/SVYDFFVWL (priming)-DC/ SVYDFFVWL (boosting) group,and 98. 90%+/-0.90% and 1.05%+/-0.21% in Ad hTRP2 (priming)-DC/ SVYDFFVWI, (boosting) group, respectively. In the tumor-bearing model, none of mice survived in DC/SVYDFFVWL (priming)-DC/SVYDFFVWL (boosting) group, and just only 40% of mice were tumor-free in Ad hTRP2 (priming) -Ad hTRP2 (boosting) group, whereas 100% of mice survived in Ad hTRP2 (priming)-DC/SVYDFFVWL (boosting) group.


CONCLUSIONS
Boosting with DC/ SVYDFFVWL can significantly enhance the immunity against melanomas elicited by priming with Ad hTRP2, indicating that first priming with Ad hTRP2 and then boosting with DC/SVYDFFVWL is a potentially effective regimen for overcoming the disadvantage that anti-tumor immune response can not be significantly increased by readministration of adenovirus.
Tan
Xiao-hua
XH
Department of Hematology, Beijing Military District General Hospital, Beijing 100700, China. xiaohua_t@hotmail.com
Liu
Chang
C
Wan
Yong-hong
YH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D019746:Intramolecular Oxidoreductases / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines; D008565:Membrane Proteins; D010446:Peptide Fragments; C500290:peptide SVYDFFVWL; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase