Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma

Rachel Lubong Sabado, Anna Pavlick, Sacha Gnjatic, Crystal M. Cruz, Isabelita Vengco, Farah Hasan, Meredith Spadaccia, Farbod Darvishian, Luis Chiriboga, Rose Marie Holman, Juliet Escalon, Caroline Muren, Crystal Escano, Ethel Yepes, Dunbar Sharpe, John P. Vasilakos, Linda Rolnitzsky, Judith D. Goldberg, John Mandeli, Sylvia AdamsAchim Jungbluth, Linda Pan, Ralph Venhaus, Patrick A. Ott, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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.

Original languageEnglish
Pages (from-to)278-287
Number of pages10
JournalCancer Immunology Research
Volume3
Issue number3
DOIs
StatePublished - Mar 2015

Fingerprint

Dive into the research topics of 'Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma'. Together they form a unique fingerprint.

Cite this