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- Title
Tumor-associated antigen/IL-21-transduced dendritic cell vaccines enhance immunity and inhibit immunosuppressive cells in metastatic melanoma.
- Authors
Aravindaram, K; Wang, P-H; Yin, S-Y; Yang, N-S
- Abstract
Dendritic cell (DC)-based vaccine approaches are being actively evaluated for developing immunotherapeutic agents against cancers. In this study, we investigated the use of engineered DCs expressing transgenic tumor-associated antigen hgp100 and the regulatory cytokine interleukin-21, namely DC-hgp100/mIL-21, as a therapeutic vaccine against melanoma. Tumor-bearing mice were injected intratumorally with transgenic DCs followed by three booster injections. Transgenic DC-hgp100/mIL-21 showed significant reduction in primary tumor growth and metastasis compared with DC-hgp100 alone and DC-mIL-21 alone. In vivo depletion of specific immune cell types (CD8+ T, CD4+ T and Natural killer (NK)-1.1+ cells) effectively blocked the protective effect of this combinational vaccine. In adoptive transfer experiments, a survival rate of nearly 90% was observed at 60 days post-tumor inoculation for the combinational vaccine group. In contrast, all mice in the DC-hgp100 and DC-mIL-21-only groups died within 43-46 days after tumor challenge. Considerably increased levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, granulocyte macrophage colony-stimulating factor (GM-CSF) and cytotoxic T lymphocytes (CTLs) were detected with the combination vaccine group compared with other individual treatment groups. In comparison with the DC-hgp100 or mIL-21 groups, the combinational DC-hgp100/mIL-21 vaccine also drastically suppressed the myeloid-derived suppressor cells (MDSCs) and T-regulatory (Treg) cell populations. Our findings suggest that a combinational DC- and gene-based hgp100 and mIL-21 vaccine therapy strategy warrants further evaluation as a clinically relevant cancer vaccine approach for human melanoma patients.
- Subjects
TUMOR antigens; CANCER immunotherapy; INTERLEUKIN-21; DENDRITIC cells; CELLULAR signal transduction; IMMUNOSUPPRESSIVE agents; GENETIC engineering; CANCER vaccines
- Publication
Gene Therapy, 2014, Vol 21, Issue 5, p457
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/gt.2014.12