Comparative analysis of cytotoxic T lymphocyte response induced by dendritic cells pulsed with recombinant adeno-associated virus carrying α-fetoprotein gene or cancer cell lysate

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and difficult to treat types of cancer worldwide. Antigen-targeted immunotherapy has the potential to be a novel and effective adjuvant for use in HCC. In the present study, recombinant adeno-associated virus carrying the α-fetoprotein gene (rAAV/AFP) and cancer cell lysates were used to pulse antigen-presenting dendritic cells (DCs) in order to stimulate a cytotoxic T lymphocyte (CTL) response against HCC. rA AV/AFP-pulsed and cancer cell lysate-pulsed DCs resulted in a mature DC phenotype with high expression of major histocompatibility complex (MHC) class I, MHC class II, CD80, CD83 and CD86 molecules. However, rAAV/AFP-pulsed DCs exhibited superiority over cancer cell lysate-pulsed DCs in terms of stimulating proliferation of T cells, activating T cells to secret interferon-γ (IFN-γ) and inducing an AFP-specific MHC class I-restricted CTL response. The current data suggest that pulsing of DCs using rAAV/AFP is more effective than the cancer cell lysate-pulsing technique, and that this technique may be used for the development of immunotherapy in AFP-positive HCC.