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.

Jeong-Im Sin, Ha Kim, Euri Ahn, Yong Hwan Jeon, Won Sun Park, Sang-Yeul Lee, Byungsuk Kwon

Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea. jsin1964@hanmail.net

Cancer letters 2013 Apr 28

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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, 7mm). 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. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Citation

Jeong-Im Sin, Ha Kim, Euri Ahn, Yong Hwan Jeon, Won Sun Park, Sang-Yeul Lee, Byungsuk Kwon. 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. Cancer letters. 2013 Apr 28;330(2):190-9