Glycolipid-anchored IL-12 expressed on tumor cell surface induces antitumor immune response.
Systemic or local administration of cytokine has been used as a mode to enhance the antitumor immune response induced by many cancer vaccines. We have investigated whether the expression of cytokines on the tumor cell surface as a glycolipid (GPI)-anchored form will be effective in inducing antitumor immune response using a GPI-anchored interleukin (IL)-12 (GPI-IL-12) as a model. GPI-IL-12-induced the proliferation of concanavalin A-activated T cells and induced IFN-gamma secretion by activated and allogeneic T cells, indicating that the membrane-expressed IL-12 can stimulate T cells. GPI-IL-12 expressed on the tumor cell surface prevented tumor growth in mice in a highly tumorigenic murine mastocytoma model. These results suggest that the cell surface-expressed GPI-IL-12 can be effective in inducing antitumor immune response, and GPI-anchored cytokines expressed on the tumor cell surface may be a novel approach to deliver cytokines at the immunization site during vaccination against cancer. Furthermore, purified GPI-anchored cytokines can be used to quickly modify tumor membranes by the protein transfer method to express the desired cytokines for vaccine development.
Nagarajan
Shanmugam
S
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Selvaraj
Periasamy
P
D000818:Animals; D018957:CD59 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D012515:Mast-Cell Sarcoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D011993:Recombinant Fusion Proteins; D018664:Interleukin-12; D007371:Interferon-gamma