Combined vaccination with NY-ESO-1 protein, poly-ICLC, and montanide improves humoral and cellular immune responses in patients with high-risk melanoma

Anna Pavlick, Ana B. Blazquez, Marcia Meseck, Michael Lattanzi, Patrick A. Ott, Thomas U. Marron, Rose Marie Holman, John Mandeli, Andres M. Salazar, Christopher B. McClain, Gustavo Gimenez, Sreekumar Balan, Sacha Gnjatic, Rachel Lubong Sabado, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Given its ability to induce both humoral and cellular immune responses, NY-ESO-1 has been considered a suitable antigen for a cancer vaccine. Despite promising results from early-phase clinical studies in patients with melanoma, NY-ESO-1 vaccine immunotherapy has not been widely investigated in larger trials; consequently, many questions remain as to the optimal vaccine formulation, predictive biomarkers, and sequencing and timing of vaccines in melanoma treatment. We conducted an adjuvant phase I/II clinical trial in high-risk resected melanoma to optimize the delivery of poly-ICLC, a TLR-3/MDA-5 agonist, as a component of vaccine formulation. A phase I dose-escalation part was undertaken to identify the MTD of poly-ICLC administered in combination with NY-ESO-1 and montanide. This was followed by a randomized phase II part investigating the MTD of poly-ICLC with NY-ESO-1 with or without montanide. The vaccine regimens were generally well tolerated, with no treatment-related grade 3/4 adverse events. Both regimens induced integrated NY-ESO-1–specific CD4þ T-cell and humoral responses. CD8þ T-cell responses were mainly detected in patients receiving montanide. T-cell avidity toward NY-ESO-1 peptides was higher in patients vaccinated with montanide. In conclusion, NY-ESO-1 protein in combination with poly-ICLC is safe, well tolerated, and capable of inducing integrated antibody and CD4þ T-cell responses in most patients. Combination with montanide enhances antigen-specific T-cell avidity and CD8þ T-cell cross-priming in a fraction of patients, indicating that montanide contributes to the induction of specific CD8þ T-cell responses to NY-ESO-1.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalCancer Immunology Research
Volume8
Issue number1
DOIs
StatePublished - 2020

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