alpha-Fetoprotein-specific tumor immunity induced by plasmid prime-adenovirus boost genetic vaccination

Cancer Res. 2001 Dec 15;61(24):8782-6.

Abstract

alpha-Fetoprotein (AFP) is a potential target for immunotherapy in hepatocellular carcinoma; both the murine and human T-cell repertoires can recognize AFP-derived epitopes in the context of the MHC. Protective immunity can be generated with AFP-engineered dendritic cell-based vaccines. We now report a DNA-based immunization strategy using a prime-boost approach: coadministration of plasmid DNA encoding murine AFP and murine granulocyte-macrophage colony-stimulating factor followed by boosting with an AFP-expressing nonreplicating adenoviral vector. This immunization strategy can elicit a high frequency of Th1-type AFP-specific cells leading to tumor protective immunity in mice at levels comparable with AFP-engineered dendritic cells. This cell-free mode of immunization is better suited for large-scale vaccine efforts for patients with hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cancer Vaccines / genetics*
  • Cancer Vaccines / immunology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / therapy*
  • Epitopes, T-Lymphocyte / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology*
  • Immunotherapy, Active / methods
  • Jurkat Cells / immunology
  • Jurkat Cells / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology
  • Liver Neoplasms / therapy*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Plasmids / genetics
  • T-Lymphocytes / immunology
  • Transfection
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • alpha-Fetoproteins / biosynthesis
  • alpha-Fetoproteins / genetics*
  • alpha-Fetoproteins / immunology*

Substances

  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Immunodominant Epitopes
  • Peptide Fragments
  • Vaccines, DNA
  • alpha-Fetoproteins
  • Granulocyte-Macrophage Colony-Stimulating Factor