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.
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.
Song
S
S
Department of Molecular Biology and Key Laboratory of Experimental Animal, Hebei Medical University, Medical experimental Center, People's Hospital of Hebei Province, Shijiazhuang, China.
Zhang
K
K
You
H
H
Wang
J
J
Wang
Z
Z
Yan
C
C
Liu
F
F
D000818:Animals; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D015226:Dinucleoside Phosphates / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000379:methods
D019496:Cancer Vaccines; D015226:Dinucleoside Phosphates; D006512:Hepatitis B Core Antigens; D007371:Interferon-gamma; D053699:Interleukin-7 Receptor alpha Subunit; C015772:CpG dinucleotide