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[Cancer Research 64, 6783-6790, September 15, 2004]
© 2004 American Association for Cancer Research


Immunology

Dendritic Cells Strongly Boost the Antitumor Activity of Adoptively Transferred T Cells In vivo

Yanyan Lou1, Gang Wang1, Gregory Lizée1, Grace J. Kim1, Steven E. Finkelstein2, Chiguang Feng2, Nicholas P. Restifo2 and Patrick Hwu1

1 Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and 2 National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Dendritic cells (DCs) have been well characterized for their ability to initiate cell-mediated immune responses by stimulating naive T cells. However, the use of DCs to stimulate antigen-activated T cells in vivo has not been investigated. In this study, we determined whether DC vaccination could improve the efficacy of activated, adoptively transferred T cells to induce an enhanced antitumor immune response. Mice bearing B16 melanoma tumors expressing the gp100 tumor antigen were treated with cultured, activated T cells transgenic for a T-cell receptor specifically recognizing gp100, with or without concurrent peptide-pulsed DC vaccination. In this model, antigen-specific DC vaccination induced cytokine production, enhanced proliferation, and increased tumor infiltration of adoptively transferred T cells. Furthermore, the combination of DC vaccination and adoptive T-cell transfer led to a more robust antitumor response than the use of each treatment individually. Collectively, these findings illuminate a new potential application for DCs in the in vivo stimulation of adoptively transferred T cells and may be a useful approach for the immunotherapy of cancer.




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