Ad hTRP2 - mediated immunity against melanoma is enhanced by dendritic cells pulsed with peptide.
- Author:
Xiao-hua TAN
1
;
Chang LIU
;
Yong-hong WAN
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Animals; CD8-Positive T-Lymphocytes; immunology; Cancer Vaccines; immunology; Cell Line, Tumor; Cells, Cultured; Cytotoxicity Tests, Immunologic; Dendritic Cells; cytology; immunology; Female; Genetic Vectors; genetics; Humans; Immunization, Secondary; methods; Intramolecular Oxidoreductases; immunology; Melanoma, Experimental; immunology; pathology; therapy; Membrane Proteins; immunology; Mice; Mice, Inbred C57BL; Peptide Fragments; immunology; Survival Analysis; T-Lymphocytes, Cytotoxic; immunology
- From: Chinese Journal of Oncology 2006;28(9):658-661
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSThe 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.
RESULTSThe 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.
CONCLUSIONBoosting 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.
