Induction of alpha-fetoprotein-specific CD4- and CD8-mediated T-cell response using RNA-transfected dendritic cells.
alpha-Fetoprotein (AFP) may be a possible target for a hepatocellular carcinoma (HCC)-specific vaccination. But some studies have demonstrated that dendritic cells (DCs) treated with AFP become dysfunctional. So in this study, we try to transfect AFP mRNA into DCs and observe the ability of DCs to induce AFP-specific CD4(+) and CD8(+) T cells. We hope that AFP can be processed and presented by DCs directly, rather than released to the cultures. So there will be no AFP negative effect on the function of DCs. In the study, immature DCs generated from peripheral blood mononuclear cells (PBMCs) of HLA-A2(+) HCC patients were transfected with AFP mRNA. Then the transfected, matured DCs were used to stimulate autologous T cells. The results showed that the expressions of membrane molecules of DCs after transfection were increased dramatically, and interleukin-12 (IL-12) p70 release in the supernatant was elevated significantly. There was only a minority of AFP release in the supernatants of transfected DCs. CTLs induced by the transfected DCs recognized HLA-matched AFP positive HepG2 cell line specifically and the AFP-specific proliferative T-cell responses could also be induced. These findings indicate that this AFP mRNA transfection strategy could generate fully functional DCs, which could induce specific T cells to recognize AFP(+) HCC cells.
Zhang
Hong-Mei
HM
Center of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Zhang
Li-Wang
LW
Ren
Jun
J
Fan
Li
L
Si
Xiao-Ming
XM
Liu
Wen-Chao
WC
D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology*; D012313:RNA / Q000235:genetics; D014162:Transfection; D000509:alpha-Fetoproteins / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D000509:alpha-Fetoproteins; D012313:RNA