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Significant anti-tumour activity of adoptively transferred T cells elicited by intratumoral dendritic cell vaccine injection through enhancing the ratio of CD8(+) T cell/regulatory T cells in tumour

S Song, K Zhang, H You, J Wang, Z Wang, C Yan, F Liu
Clinical and Experimental Immunology 2010, 162 (1): 75-83
20735440
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.

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