Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors

Clin Immunol. 2016 May;166-167:48-58. doi: 10.1016/j.clim.2016.03.015. Epub 2016 Apr 9.

Abstract

We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.

Keywords: Cyclophosphamide; Five-peptide cancer vaccine; Regulatory T cells; Translational research.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / immunology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / immunology*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epitopes / administration & dosage
  • Epitopes / immunology
  • Female
  • HLA-A24 Antigen / genetics
  • HLA-A24 Antigen / immunology
  • Humans
  • Kaplan-Meier Estimate
  • Leukopenia / chemically induced
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Peptides / administration & dosage
  • Peptides / immunology
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology*

Substances

  • Cancer Vaccines
  • Epitopes
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • Peptides
  • Vaccines, Subunit
  • Cyclophosphamide