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, 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
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 CD4+ T-cell and humoral responses. CD8+ 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 CD4+ T-cell responses in most patients. Combination with montanide enhances antigen-specific T-cell avidity and CD8+ T-cell cross-priming in a fraction of patients, indicating that montanide contributes to the induction of specific CD8+ T-cell responses to NY-ESO-1.
Conflict of interest statement
Conflict of interest: NB is on the SAB of Neon Therapeutics, Tempest, and Check Point Sciences, and a consultant for Genentech. NB also receives research support from Merck. R.S. works as clinical scientist at Genentech, Inc. No potential conflicts of interest were disclosed by other authors.
©2019 American Association for Cancer Research.
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Source: PubMed