Dendritic cells pulsed with hsp70-peptide complexes derived from human hepatocellular carcinoma induce specific anti-tumor immune responses

Abstract

To investigate the anti-tumor effect of dendritic cells (DCs) pulsed with hsp70-peptide complexes derived from human hepatocellular carcinoma (HCC) cells on human T cells. Hsp70-peptide complexes were purified from human HCC cells with column chromatography using ADP-agarose and DEAE-Sepharose. DCs were derived from peripheral blood mononuclear cells of healthy donors in the presence of human GM-CSF and IL-4. The anti-tumor effect of DCs pulsed with hsp70-peptide complexes on human T-cell was assayed by CTL and enzyme-linked immunospot (ELISPOT) tests. Hsp70-peptide complexes derived from human HCC cells activated phenotypic and functional maturation of DCs. The matured DCs stimulated a high level of autologous T-cell proliferation and type I cytokine secretion, and induced HCC-specific cytotoxic T lymphocytes (CTLs), which specifically killed HCC cells by a MHC class I restricted mechanism. Hsp70-peptide complexes derived from human HCC cells can serve as a potent tumor antigen source for pulsing DCs, the pulsed DCs are very effective in activating specific T-cell responses against HCC cells.