Antitumor immune responses derived from transgenic expression of CD40 ligand in myeloma cells.
Tumor cells engineered to express immunogenes have been used for cancer vaccines to induce the antitumor immunity and study the antitumor immune mechanisms derived from the immunogene expression. In the present study, we engineered a mouse myeloma cell line J558 with a cloned CD40 ligand (CD40L) gene. We demonstrated that (i) the engineered J558/CD40L tumor cells expressing the CD40 ligand molecule lost their tumorigenicity in syngeneic mice, and (ii) the inoculation of J558/CD40L tumor cells further lead to the protective immunity against wild-type J558 tumors. In animal studies using T-cell subset depleted mice, we further showed that the primary rejection of J558/CD40L tumors did not require T cells, but was mainly mediated by NK cells, whereas the effector phase of the protective immunity is mediated by CD8+ T cells. In addition, our data, for the first time, showed that the inoculation of engineered J558/CD40L tumor cells is able to stimulate stronger activation of dendritic cells with enhanced expression of B7-1 and ICAM-1 molecules than the wild-type J558 tumor cells Taken together, we demonstrated the antitumor effect of engineered J558/CD40L tumor cells that is mediated by the activation of the host dendritic cells in vivo. Our data indicate that the introduction of co-stimulatory CD40 ligand molecule will be useful as a new strategy of immunogene therapy against tumors.
Liu
Yongqing
Y
Saskatoon Cancer Center, Department of Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W0, Canada.
Qureshi
Mabood
M
Xiang
Jim
J
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors; D007109:Immunity; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation
D018122:B7-1 Antigen; D018076:DNA, Complementary; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand