Comparative analysis of DC fused with allogeneic hepatocellular carcinoma cell line HepG2 and autologous tumor cells as potential cancer vaccines against hepatocellular carcinoma.
Fusions of patient-derived dendritic cells (DCs) and autologous tumor cells induce T-cell responses against autologous tumors in animal models and human clinical trials. These fusion cells require patient-derived tumor cells, which are not, however, always available. Here we fused autologous DCs from patients with hepatocellular carcinoma (HCC) to an allogeneic HCC cell line (HepG2). These fusion cells co-expressed tumor-associated antigens (TAAs) and DC-derived costimulatory and MHC molecules. Both CD4(+) and CD8(+) T cells were activated by the fusion cells. Cytotoxic T lymphocytes (CTLs) induced by the fusion cells were able to kill autologous HCC by HLA-A2- and/or HLA-A24-restricted mechanisms. CTL activity against shared TAAs indicates that the presence of alloantigens does not prevent the development of CTLs with activity against autologous HCC cells. These fusion cells may have applications in anti-tumor immunotherapy through cross-priming against shared tumor antigens and may provide a platform for adoptive immunotherapy.
Cao
Da-Yong
DY
Department of Hepatobiliary Surgery, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Shaanxi Province, China.
Yang
Jing-Yue
JY
Yue
Shu-Qiang
SQ
Tao
Kai-Shan
KS
Song
Zhen-Shun
ZS
Wang
De-Sheng
DS
Yang
Yan-Ling
YL
Dou
Ke-Feng
KF
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000628:therapy; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology* / Q000628:therapy
D019496:Cancer Vaccines; C508609:IL10 protein, human; C508598:IL4 protein, human; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma