Combined Vaccination with NY-ESO-1 Protein, Poly-ICLC, and Montanide Improves Humoral and Cellular Immune Responses in Patients with High-Risk Melanoma. Academic Article uri icon

Overview

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.

authors

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

publication date

  • November 7, 2019

Research

keywords

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Carboxymethylcellulose Sodium
  • Immunity, Cellular
  • Immunity, Humoral
  • Mannitol
  • Melanoma
  • Membrane Proteins
  • Oleic Acids
  • Poly I-C
  • Polylysine

Identity

PubMed Central ID

  • PMC6946846

Scopus Document Identifier

  • 85077669992

Digital Object Identifier (DOI)

  • 10.1016/S1470-2045(15)70122-1

PubMed ID

  • 31699709

Additional Document Info

volume

  • 8

issue

  • 1