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

Cancer Immunol Res. 2020 Jan;8(1):70-80. doi: 10.1158/2326-6066.CIR-19-0545. Epub 2019 Nov 7.


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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Aged
  • Antigens, Neoplasm / administration & dosage*
  • Antigens, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Carboxymethylcellulose Sodium / administration & dosage
  • Carboxymethylcellulose Sodium / analogs & derivatives*
  • Cross-Priming / immunology
  • Female
  • Humans
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • Interferon Inducers / administration & dosage
  • Male
  • Mannitol / administration & dosage
  • Mannitol / analogs & derivatives*
  • Melanoma / immunology*
  • Melanoma / therapy
  • Membrane Proteins / administration & dosage*
  • Membrane Proteins / immunology
  • Middle Aged
  • Oleic Acids / administration & dosage*
  • Patient Safety
  • Poly I-C / administration & dosage*
  • Polylysine / administration & dosage
  • Polylysine / analogs & derivatives*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Interferon Inducers
  • Membrane Proteins
  • Oleic Acids
  • montanide ISA 51
  • Polylysine
  • Mannitol
  • poly ICLC
  • Carboxymethylcellulose Sodium
  • Poly I-C