New designs for cancer vaccine and artificial veto cells: an emerging palette of protein paints.
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.
Tykocinski
Mark L
ML
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. mlt4@mail.med.upenn.edu
Chen
Aoshuang
A
Huang
Jui-Han
JH
Weber
Matthew C
MC
Zheng
Guoxing
G
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D015202:Protein Engineering / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines; D007376:Interleukin-2; D008565:Membrane Proteins