Combined stimulation of TLR9 and 4.1BB augments Trp2 peptide vaccine-mediated melanoma rejection by increasing Ag-specific CTL activity and infiltration into tumor sites

Peptide vaccines are a clinically applicable therapy shown to be effective in tumor control. In this study, Trp2 peptides plus CpG-oligodeoxynucleotide treatment was found to induce Ag-specific IFN-γ and CD8+ CTL responses, and antitumor activity against large established melanoma (tumor size, 7 mm). A combination of anti-4.1BB antibodies with Trp2 peptides + CpG-oligodeoxynucleotide increased the antitumor cure 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.

► Trp2 peptides plus CpG-oligodeoxynucleotide treatment in combination with anti-4.1BB Abs dramatically increases antitumor cure rates. ► Trp2 peptides plus CpG-oligodeoxynucleotide treatment in combination with anti-4.1BB Abs augments Ag-specific CD8+ CTL responses. ► The augmented Ag-specific CD8+ CTLs are associated with their subsequent infiltration into the tumor sites. ► Trp2 peptide-mediated tumor eradication requires combined stimulation of TLR9 by CpG-oligodeoxynucleotide and 4.1BB by anti-4.1BB Abs.