We have shown that immunization with dendritic cells (DCs) pulsed with hepatitis B virus core
antigen virus-like particles (HBc-VLP) packaging with
cytosine-guanine dinucleotide (CpG) (HBc-VLP/CpG) alone were able to delay
melanoma growth but not able to eradicate the established tumour in mice. We tested whether, by modulating the vaccination approaches and injection times, the anti-tumour activity could be enhanced. We used a B16-HBc
melanoma murine model not only to compare the efficacy of DC
vaccine immunized via footpads, intravenously or via intratumoral
injections in treating
melanoma and priming tumour-specific immune responses, but also to observe how DC vaccination could improve the efficacy of adoptively transferred T cells to induce an enhanced anti-tumour immune response. Our results indicate that, although all vaccination approaches were able to protect mice from developing
melanoma, only three intratumoral
injections of DCs could induce a significant anti-tumour response. Furthermore, the combination of intratumoral DC vaccination and adoptive T cell transfer led to a more robust anti-tumour response than the use of each treatment individually by increasing CD8(+) T cells or the ratio of CD8(+) T cell/regulatory T cells in the tumour site. Moreover, the combination vaccination induced tumour-specific immune responses that led to tumour regression and protected surviving mice from tumour rechallenge, which is attributed to an increase in CD127-expressing and
interferon-γ-producing CD8(+) T cells. Taken together, these results indicate that repeated intratumoral DC vaccination not only induces expansion of
antigen-specific T cells against tumour-associated
antigens in tumour sites, but also leads to elimination of pre-established tumours, supporting this combined approach as a potent strategy for DC-based
cancer immunotherapy.