Abstract
Tumor antigen gene-modified dendritic cells (DC) generates robust antigen-specific protective antitumor responses. Though the role of CD4 positive and CD8 positive cells in the immunological response to gene-modified DC has been well-characterized, the role of NK cells in this response has been somewhat less clear. Owing to the significant contribution of innate immunity in other model systems, we postulated that NK cells would hold a critical position in the generation of an immune response following immunization with tumor antigen-engineered DC. Immunization with MART-1 melanoma antigen-engineered DC in C57BL/6 mice resulted in the generation of antigen-specific cytotoxic T lymphocytes and in vivo protective responses to the murine B16 melanoma. These responses were dependent on the presence of functional NK cells, although NK cells alone were not sufficient in generating protective responses. Adoptive transfer of NK cells into an NK-deficient but T-cell-competent environment restored the protective response to gene-modified DC immunization. In conclusion, protective immunity after tumor antigen gene-modified DC immunization requires collaboration between CD4+ and CD8+ T cells and NK cells.
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Acknowledgements
This work was supported by NIH/NCI grants RO1 CA77623, RO1 CA79976, RO1 CA75956, and K12 CA 76905 (all to JSE). LHB is a recipient of a UCLA Human Gene Medicine Seed Grant and American Heart Association Career Development Award #0330102N. AR is a recipient of an American Society of Clinical Oncology Career Development Award, a Career Development Award from Stop Cancer and K23 CA93376.
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Wargo, J., Schumacher, L., Comin-Anduix, B. et al. Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells. Cancer Gene Ther 12, 516–527 (2005). https://doi.org/10.1038/sj.cgt.7700818
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DOI: https://doi.org/10.1038/sj.cgt.7700818
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