Induction of HLA-A2-restricted CTL responses by a tubular structure carrying human melanoma epitopes

Vaccine. 2002 Jun 7;20(19-20):2463-73. doi: 10.1016/s0264-410x(02)00185-8.

Abstract

Epitope-based vaccination strategies designed to induce strong tumor-specific CD8(+) T cell responses are being widely considered for cancer immunotherapy. Here, two recombinant tubular structures, NS1-Mela 1 and NS1-Mela 2, carrying, respectively two HLA-A2 epitopes derived from human melanoma antigens were constructed and their capability to induce CTL responses in vivo were studied in HLA-A2 transgenic mice. Strong CTL responses specific for GnT-V/NA 17-A and gp100 (154-162) epitopes were generated in HLA-A2 transgenic mice immunized by the construct NS1-Mela l carrying these two epitopes. The second construct NS1-Mela 2 carrying both Tyrosinase (369-377Da) and Melan-A/Mart-1 (27-35) epitopes induced a weak Tyrosinase-specific CTL response in mice but failed to induce specific CTL responses against the Melan-A/Mart-1 (27-35) epitope in the tested mice. Thus, recombinant tubular structures containing multiple tumoral epitopes may lead to new strategies for the induction of strong tumor-specific CTL responses in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Baculoviridae / genetics
  • Base Sequence
  • Blotting, Western
  • Cancer Vaccines / immunology
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology*
  • HLA-A2 Antigen / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Melanoma / immunology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Cancer Vaccines
  • DNA Primers
  • Epitopes
  • HLA-A2 Antigen
  • Interferon-gamma