Th1 cell adjuvant therapy combined with tumor vaccination: a novel strategy for promoting CTL responses while avoiding the accumulation of Tregs.

概要

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We have previously described a method for adoptive immunotherapy of cancer based on antigen-specific Th1 cells. However, efficient induction of anti-tumor responses using Th1 cells remains a formidable challenge, especially for MHC class II-negative tumors. In the present study, we sought to develop a novel strategy to eradicate established tumors of the MHC class II-negative, ovalbumin (OVA)-expressing EG-7 cells. Tumor-bearing mice were intradermally treated with OVA-specific Th1 cells, combined with the model tumor antigen (OVA), near the tumor-draining lymph node (DLN). We found that tumor growth was significantly inhibited by this strategy and 50–60% of tumor-bearing mice were completely cured. Tumor eradication was crucially dependent on the generation of OVA/H-2Kb-specific CTLs in the tumor DLNs and tumor site. The injected Th1 cells were mainly distributed in tumor DLNs, where they vigorously proliferated and enhanced the activation of dendritic cells. Strikingly, we also found that the accumulation of CD4+CD25+ regulatory T cells (Tregs) was significantly inhibited in tumor DLNs by Th1 cell adjuvant therapy and this abrogation was associated with IFN secreted by Th1 cells. These results identify Th1 cell adjuvant therapy combined with tumor vaccination as a novel approach to the treatment of human cancer.
2007-02-01