Induction of MAGE-A3 and HPV-16 Immunity by Trojan Vaccines in Patients With Head and Neck Carcinoma

Head Neck. 2012 Dec;34(12):1734-46. doi: 10.1002/hed.22004. Epub 2012 Jan 27.

Abstract

Background: We performed a pilot study using Trojan vaccines in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). These vaccines are composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or human papillomavirus (HPV)-16 derived peptides, joined by furin-cleavable linkers, and linked to a "penetrin" peptide sequence derived from HIV-TAT. Thirty-one patients with SCCHN were screened for the trial and 5 were enrolled.

Methods: Enrolled patients were treated with 300 μg of Trojan peptide supplemented with Montanide and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 4-week intervals for up to 4 injections.

Results: Following vaccination, peripheral blood mononuclear cells (PBMCs) from 4 of 5 patients recognized both the full Trojan constructs and constituent HLA-II peptides, whereas responses to HLA-I restricted peptides were less pronounced.

Conclusion: This treatment regimen seems to have acceptable toxicity and elicits measurable systemic immune responses against HLA-II restricted epitopes in a subset of patients with advanced SCCHN.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / therapy*
  • Carcinoma, Squamous Cell / virology
  • Epitopes / immunology*
  • Epitopes, T-Lymphocyte
  • Female
  • HLA-A2 Antigen / immunology
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / therapy*
  • Head and Neck Neoplasms / virology
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / immunology
  • Pilot Projects
  • Polymerase Chain Reaction
  • Squamous Cell Carcinoma of Head and Neck
  • T-Lymphocytes, Cytotoxic / immunology
  • Virus Activation

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Epitopes, T-Lymphocyte
  • HLA-A*02 antigen
  • HLA-A2 Antigen
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Interferon-gamma