title: Lymphotactin gene-modified bone marrow dendritic cells act as more potent adjuvants for peptide delivery to induce specific antitumor immunity.
abstract: Dendritic cells (DC) are regarded as attractive candidates for cancer immunotherapy. Our aim is to improve the therapeutic efficacy of DC-based tumor vaccine by augmenting DC preferential chemotaxis on T cells. Mouse bone marrow-derived DC were transduced with lymphotactin (Lptn) gene by adenovirus vector. The supernatants from Lptn gene-modified DC (Lptn-DC) were capable of attracting CD4+ and CD8+ T cells in a chemotaxis assay, whereas their mock control could not. Lptn expression of Lptn-DC was further confirmed by RT-PCR. Lptn-DC were pulsed with Mut1 peptide and used for vaccination. Immunization with the low dose (1 x 10(4)) of Mut1 peptide-pulsed DC induced weak CTL activity, whereas the same amounts of Mut1 peptide-pulsed Lptn-DC markedly induced specific CTL against 3LL tumor cells. A single immunization with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC could render mice resistant to a 5 x 10(5) 3LL tumor cell challenge completely, but their counterpart could not. The protective immunity induced by Mut1 peptide-pulsed Lptn-DC depends on both CD4+ T cells and CD8+ T cells rather than NK cells in the induction phase and depends on CD8+ T cells rather than CD4+ T cells and NK cells in the effector phase. Moreover, the involvement of CD28/CTLA4 costimulation pathway and IFN-gamma are also necessary. When 3LL tumor-bearing mice were treated with 1 x 10(4) Mut1 peptide-pulsed Lptn-DC, their pulmonary metastases were significantly reduced, whereas the same low dose of Mut1 peptide-pulsed DC had no obvious therapeutic effects. Our data suggest that Lptn-DC are more potent adjuvants for peptide delivery to induce protective and therapeutic antitumor immunity.
authors.affiliation: Department of Immunology, Second Military Medical University, Shanghai, People's Republic of China. caoxt@public3.sta.net.cn
authors.forename: X
authors.initials: X
authors.lastname: Cao
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.forename: Q
authors.initials: Q
authors.lastname: Tao
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Hamada
authors.forename: J
authors.initials: J
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000821:virology; D016026:Bone Marrow Transplantation; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000628:therapy; D002460:Cell Line; D019744:Chemokines, C; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000378:metabolism* / Q000637:transplantation / Q000821:virology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007279:Injections, Subcutaneous; D008212:Lymphocyte Depletion / Q000379:methods; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D019744:Chemokines, C; D008222:Lymphokines; C096894:MUT 1 peptide; D009842:Oligopeptides; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C486249:Xcl1 protein, mouse; C018997:lymphotactin