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Clin Exp Immunol. 2010 Oct;162(1):75-83. doi: 10.1111/j.1365-2249.2010.04226.x.

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.

Author information

1
Department of Molecular Biology and Key Laboratory of Experimental Animal, Hebei Medical University, Medical experimental Center, People's Hospital of Hebei Province, Shijiazhuang, China.

Abstract

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.

PMID:
20735440
PMCID:
PMC2990932
DOI:
10.1111/j.1365-2249.2010.04226.x
[Indexed for MEDLINE]
Free PMC Article

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