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

Y Lou, G Wang, G Lizée, GJ Kim, SE Finkelstein… - Cancer research, 2004 - AACR
Y Lou, G Wang, G Lizée, GJ Kim, SE Finkelstein, C Feng, NP Restifo, P Hwu
Cancer research, 2004AACR
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 …
Abstract
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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