Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma Journal Article
| Authors: | Sabado, R. L.; Pavlick, A.; Gnjatic, S.; Cruz, C. M.; Vengco, I.; Hasan, F.; Spadaccia, M.; Darvishian, F.; Chiriboga, L.; Holman, R. M.; Escalon, J.; Muren, C.; Escano, C.; Yepes, E.; Sharpe, D.; Vasilakos, J. P.; Rolnitzsky, L.; Goldberg, J. D.; Mandeli, J.; Adams, S.; Jungbluth, A.; Pan, L.; Venhaus, R.; Ott, P. A.; Bhardwaj, N. |
| Article Title: | Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma |
| Abstract: | The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 μg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-μg NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4+T-cell responses. CD8+ T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8+ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4+ T-cell responses in the majority of patients; the small proportion of CD8+ T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1 -specific CD8+ T-cell responses. © 2015 American Association for Cancer Research. |
| Journal Title: | Cancer Immunology Research |
| Volume: | 3 |
| Issue: | 3 |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2015-03-01 |
| Start Page: | 278 |
| End Page: | 287 |
| Language: | English |
| DOI: | 10.1158/2326-6066.cir-14-0202 |
| PROVIDER: | scopus |
| PMCID: | PMC4374362 |
| PUBMED: | 25633712 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2016 -- Source: Scopus |
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