Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

Abstract

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 þ 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.

Induction of Primary Human T Cell Responses against Hepatitis C Virus-Derived Antigens NS3 or Core by Autologous Dendritic Cells Expressing Hepatitis C Virus Antigens: Potential for Vaccine and Immunotherapy

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Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation

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Human TFDP3, a Novel DP Protein, Inhibits DNA Binding and Transactivation by E2F

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