Abstract 2835: Combined stimulation of TLR9 and 4.1BB receptors enhances Trp2 peptide-mediated B16 melanoma regression by increasing Ag-specific CTL activity and infiltration to tumor sites.

Abstract

Abstract We previously reported that intratumoral electroporation (IT-EP) with IL-12 cDNA (IT-EP/IL12) led to the eradication of established B16 melanoma tumors in mice. Tumor eradication required the participation of CD8+ T cells, but not CD4+ T cells and NK cells. IT-EP/IL12 induced antigen-specific CD8+ T cell responses against the immunodominant Trp2180-188 epitope and generated a systemic response, resulting in significant therapeutic effects against distal, untreated tumors. In this study, we observed that when Trp2180-188 self-peptides were combined with the TLR9 agonist, CpG-oligodeoxynucleotide (ODN) for antitumor immune therapy, self-tolerance was broken, giving rise to induction of Trp2-specific CTL responses and some antitumor activity against established melanoma (7 mm in mean diameter). A combination of anti-4.1BB antibodies with Trp2 peptides plus CpG-ODN increased the antitumor regression rate from 0 to 75%. This effect was concomitant with greater induction of Ag-specific CD8+ CTLs and their infiltration into the tumor sites, highlighting the importance of combined stimulation of TLR9 and 4.1BB for achieving tumor eradication. These findings may have implications for designing peptide-based therapeutic vaccines for cancer-patients. Citation Format: Jeong-Im Sin, Hun Mo Ryoo. Combined stimulation of TLR9 and 4.1BB receptors enhances Trp2 peptide-mediated B16 melanoma regression by increasing Ag-specific CTL activity and infiltration to tumor sites. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2835. doi:10.1158/1538-7445.AM2013-2835