Enhanced tumor immunogenicity through coupling cytokine expression with antigen presentation

Xianghui He, Tom C. Tsang, Phoebe Luo, Tong Zhang, David T. Harris

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The density of tumor antigen in conjunction with major histocompatibility complex (MHC) class I molecules on the cell surface affects cytotoxic T cell (CTL) function in an active antitumor immune response. Thus, methods to enhance antigen expression/presentation could augment the effect of cancer immune therapy. In the present study, we investigated the feasibility of modifying a cytokine signal peptide with a tumor antigenic epitope. We inserted the genes encoding the MHC class I-restricted antigenic epitope of chicken ovalbumin and tyrosinase-related protein 2 into the signal sequence of the interleukin-2 gene, replacing part of the signal sequence at different positions. Our results showed that these modified signal peptides still functioned, as indicated by cytokine secretion. The antigenic epitope within the modified signal peptide could be processed properly and presented on tumor cell surface. Tumor cells demonstrated enhanced immunogenicity as indicated by increased susceptibility to CTL lysis in vitro and decreased tumor grow in vivo after gene modification. These data provide potential perspectives in designing therapeutic or vaccine strategies in immuno-gene therapy of cancer.

Original languageEnglish (US)
Pages (from-to)669-677
Number of pages9
JournalCancer gene therapy
Volume10
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Antigen presentation
  • Cytokines
  • Immunotherapy
  • Signal peptide
  • Tumor antigen

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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