Expression of co-stimulatory 4-1BB ligand induces significant tumor regression and protective immunity.
Co-stimulatory molecules play an important role in initiating antitumor immune responses. Engineered tumor cells expressing co-stimulatory molecules have been used as cancer vaccines in both experimental tumor models and clinical trials. In this study, we cloned a cDNA gene coding for the mouse co-stimulatory molecule 4-1BBL by RTPCR. The expression vector pCI-4-1BBL was constructed by DNA recombinant technology and further transfected into a moderately immunogenic EL4 and a poorly immunogenic BL6-10 tumor cell line. Expression of the co-stimulatory molecule 4-1BBL is able to induce tumor regression of EL4/4-1BBL but not BL6-10/4-1BBL tumor cell line in syngeneic BALB/c mice. The tumor regression which is mainly mediated by CD8+ T cells further leads to protective immunity against the parental EL4 tumor. Our results thus indicate the potential utility of engineered tumor cells expressing co-stimulatory molecule 4-1BBL, especially in combination with other co-stimulatory molecules such as B7-1 in cancer vaccine.
Xiang
J
J
Saskatoon Cancer Center, Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Canada.
D053330:4-1BB Ligand; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008024:Ligands; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D053330:4-1BB Ligand; D008024:Ligands; D011994:Recombinant Proteins; C505975:Tnfsf9 protein, mouse; D014409:Tumor Necrosis Factor-alpha