Tumor vaccine based on cell surface expression of DcR3/TR6.
DcR3/TR6, a secreted protein belonging to the TNF receptor superfamily, interacts with lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpes virus entrance mediator (LIGHT), Fas ligand (FasL), and TL1A, all members of the TNF superfamily. Solid-phase TR6 can trigger reverse signaling of LIGHT and FasL expressed on T cells, and lead to T cell costimulation. In this study, we engineered tumor cells to express cell surface TR6 and used these cells as a tumor vaccine. We demonstrated that mastocytoma P815 cells expressing surface TR6 (TR6-P815) effectively augmented the T cells response in vitro and ex vivo in terms of proliferation, as well as IL-2 and IFN-gamma secretion. TR6-P815 cells had reduced tumorigenicity compared with parental P815 cells. When inactivated TR6-P815 cells were employed as a vaccine, they protected the mice from challenge with live parental P815 cells, and eliminated established P815 tumors. The cell surface TR6-based tumor vaccine was also effective against low antigenicity tumors, such as B16 melanoma; co-administration of bacillus Calmette-Guérin further enhanced the vaccine's efficacy. Thus, cell surface TR6 expression is a useful addition to our tumor vaccine arsenal.
Shi
Guixiu
G
Laboratory of Immunology, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Mao
Jianning
J
Yu
Guang
G
Zhang
Jun
J
Wu
Jiangping
J
D000818:Animals; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D013601:T-Lymphocytes / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human