Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy

Cancer Immunol Immunother. 2022 Nov;71(11):2743-2755. doi: 10.1007/s00262-022-03194-5. Epub 2022 Apr 16.

Abstract

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

Keywords: Cancer vaccine; Esophageal cancer; NY-ESO-1 antigen; PIGR gene.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Cancer Vaccines*
  • Cisplatin
  • Esophageal Neoplasms*
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Fluorouracil
  • Glucans
  • Humans
  • Immunoglobulin A
  • Immunoglobulin G
  • Membrane Proteins
  • Prognosis
  • Receptors, Polymeric Immunoglobulin*

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Glucans
  • Immunoglobulin A
  • Immunoglobulin G
  • Membrane Proteins
  • Receptors, Polymeric Immunoglobulin
  • pullulan
  • Cisplatin
  • Fluorouracil