Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients

J Transl Med. 2013 Oct 5:11:246. doi: 10.1186/1479-5876-11-246.

Abstract

Background: Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001.

Methods: Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 μg or 200 μg of NY-ESO-1 protein complexed with CHP. The primary endpoints were safety and humoral immune responses, and the secondary endpoint was clinical efficacy.

Results: A total of 25 patients were enrolled. Thirteen and twelve patients were repeatedly vaccinated with 100 μg or 200 μg of CHP-NY-ESO-1 with a median of 8 or 9.5 doses, respectively. No serious adverse events related to the vaccine were observed. Three out of 13 patients in the 100-μg cohort and 7 out of 12 patients in the 200-μg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-μg cohort, an antibody response was observed in 5 out of 10 pre-antibody-negatives patients, and the antibody levels were augmented in 2 pre-antibody-positive patients after vaccination. In the 200-μg cohort, all 5 pre-antibody-negative patients became seropositive, and the antibody level was amplified in all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The patients who received 200 μg of CHP-NY-ESO-1 survived longer than patients receiving 100 μg of CHP-NY-ESO-1, even those who exhibited unresponsiveness to previous therapies or had higher tumor burdens.

Conclusions: The safety and immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 μg dose more efficiently induced immune responses and suggested better survival benefits. (Clinical trial registration number NCT01003808).

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Neoplasm / immunology
  • Antibody Formation / immunology
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cholesterol / immunology*
  • Demography
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / prevention & control
  • Female
  • Follow-Up Studies
  • Glucans / immunology*
  • Humans
  • Immunity*
  • Kaplan-Meier Estimate*
  • Male
  • Membrane Proteins / immunology*
  • Middle Aged
  • Recombinant Proteins / immunology
  • Treatment Outcome
  • Vaccination / adverse effects

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Glucans
  • Membrane Proteins
  • Recombinant Proteins
  • pullulan
  • Cholesterol

Associated data

  • ClinicalTrials.gov/NCT01003808