IFN-gamma gene transfer restores HLA-class I expression and MAGE-3 antigen presentation to CTL in HLA-deficient small cell lung cancer

Gene Ther. 1997 Oct;4(10):1029-35. doi: 10.1038/sj.gt.3300489.

Abstract

In this study, we have analyzed the possibility of inducing T cell responses against small cell lung cancer (SCLC), a still incurable tumor, by cytokine gene transfer approaches. By RT-PCR analysis most SCLC expressed the CTL-defined tumor antigens MAGE-3 (10/11), MAGE-1 (7/11) and less frequently BAGE (4/11) and GAGE1,2 (4/11). Although the surface expression of HLA class I molecules was low on most SCLC, thus preventing CTL recognition, treatment of the cells with IFN-gamma enhanced HLA-class I levels in all cases. Two MAGE3+ SCLC cell lines displaying the A2 HLA-class I allele, involved in MAGE-3 antigen presentation to CTL, were stably transfected with the IFN-gamma gene (alone or co-transfected with IL-2). IFN-gamma-transfected cells displayed a clearcut increase in expression of HLA-class I and beta 2-microglobulin at both protein and mRNA level, and of TAP-1 and TAP-2 mRNA. Perhaps more importantly, IFN-gamma transfected cells were recognized by the MAGE-3-specific A2-restricted antimelanoma CTL clone 297/22, while unmodified cells or cells transfected with the IL-2 gene alone were not. These data indicate that IFN-gamma gene transfection into HLA-deficient SCLC cells is able to restore their ability to present endogenous tumor antigens to CTL and that IFN-gamma gene transfer approaches may be attempted to induce specific CTL responses in SCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology*
  • Antigens, Neoplasm / immunology
  • Blotting, Northern
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / immunology*
  • Gene Expression
  • Gene Transfer Techniques*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Interferon-gamma / genetics*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Neoplasm Proteins / immunology*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Histocompatibility Antigens Class I
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Interferon-gamma