New designs for cancer vaccine and artificial veto cells: an emerging palette of protein paints

Immunol Res. 2003;27(2-3):565-74. doi: 10.1385/IR:27:2-3:565.

Abstract

Antigen-presenting cells (APC) can be refaced with "protein paints" that change the appearance of their T cell-oriented trans signal arrays. Our group has developed three categories of protein paints suitable for this kind of APC engineering: artificial glycosylphosphatidylinositol (GPI) proteins, palmitated-protein A:Fc*1 fusion protein conjugates, and trans signal converter proteins. Protein paints have been devised with either immune enhancement or suppression in mind. Costimulator * GPI and palmitated-protein A costimulator * Fcgamma1 conjugates can be used to augment the immune-activating potential of tumor cells. Alternatively, protein paints can be designed to transform APC into artificial veto cells, in essence creating Trojan horses capable of inhibiting pathogenic T cells. Trans signal converter proteins (TSCP) have been devised for this purpose. Our first paradigmatic inhibitory TSCP, CTLA-4 * Fas ligand, binds to APC, and in so doing, simultaneously blocks B7 costimulation (via CTLA-4) and sends inhibitory trans signals (via Fas ligand) to T cells with dramatic efficacy. Protein transfer offers a number of advantages over gene transfer in facilitating quantitative and combinatorial protein expression and simplifying in vivo applications; the palette of protein paints with immunotherapeutic potential will undoubtedly continue to evolve.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Cancer Vaccines / immunology*
  • Humans
  • Interleukin-2 / immunology
  • Lymphocyte Activation / immunology
  • Membrane Proteins / immunology*
  • Protein Engineering / methods*
  • T-Lymphocytes / immunology

Substances

  • Cancer Vaccines
  • Interleukin-2
  • Membrane Proteins