Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells.
Transduction of recombinant adenovirus into dendritic cells (DCs) is a promising new tool for cancer vaccine development. Here, we report that an adenovirus vector carrying hepatocellular carcinoma (HCC) antigen HCA661 and infected into DCs generates T-cell immunity against hepatoma cells. HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of an HCC patient. We constructed a recombinant adenovirus expressing the full-length cDNA of HCA661 gene and then transduced immature DCs, which had been generated with GM-CSF and IL-4 from peripheral blood mononuclear cell of HLA-A2(+) healthy donors. The resulting adenovirus-transduced DCs differentiated in the presence of monocyte-conditioned medium and poly [I] : poly [C], expressing the surface markers of mature DCs, including CD83, CD80, CD86 and HLA-DR. After maturation, the transduced DCs transcribed HCA661 mRNA and were able to prime the naïve T cells to become cytotoxic T lymphocytes (CTLs). Intracellular flow cytometry and enzyme-linked immunospot assay showed that these CTLs were able to target a hepatoma cell line, HepG2, which is HLA-A2 and HCA661 positive. In summary, we found that this recombinant adenovirus can help to induce DC maturation and these mature DCs can activate T cells to target hepatoma cells. Therefore, this recombinant adenovirus may have potential for use in liver cancer immunotherapy.
Chan
R C-F
RC
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Pang
X-W
XW
Wang
Y-D
YD
Chen
W-F
WF
Xie
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D003470:Culture Media; D018076:DNA, Complementary; D003713:Dendritic Cells; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation; D009000:Monocytes; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic
D000951:Antigens, Neoplasm; D003470:Culture Media; D018076:DNA, Complementary