title: Vesiculated alpha-tocopheryl succinate enhances the anti-tumor effect of dendritic cell vaccines.
abstract: Alpha tocopheryl succinate (alpha-TOS) is a non-toxic vitamin E analog under study for its anti-cancer properties. In an earlier study, we showed that alpha-TOS, when used in combination with non-matured dendritic cells (nmDC) to treat pre-established tumors, acts as an effective adjuvant. In this study, we have used vesiculated alpha-TOS (Valpha-TOS), a more soluble form of alpha-TOS that is relevant for clinical use, in combination with dendritic cells to treat pre-established murine tumors. We demonstrate that Valpha-TOS kills tumor cells in vitro and inhibits the growth of pre-established murine lung carcinoma (3LLD122) as effectively as alpha-TOS. The combination of Valpha-TOS plus non-matured or TNF-alpha-matured DC is more effective at inhibiting the growth of established tumors than Valpha-TOS alone. We also observed that Valpha-TOS induces expression of heat shock proteins in tumor cells and that co-incubation of non-matured DC with lysate derived from Valpha-TOS-treated tumor cells leads to DC maturation evidenced by up-regulation of co-stimulatory molecules and secretion of IL-12p70. This study therefore demonstrates the immunomodulatory properties of Valpha-TOS that may account for its adjuvant effect when combined with DC vaccines to treat established tumors.
authors.affiliation: Department of Microbiology and Immunology, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Lalitha V
authors.initials: LV
authors.lastname: Ramanathapuram
authors.forename: Tobias
authors.initials: T
authors.lastname: Hahn
authors.forename: Michael W
authors.initials: MW
authors.lastname: Graner
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
authors.forename: Emmanuel T
authors.initials: ET
authors.lastname: Akporiaye
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004304:Dosage Forms; D004354:Drug Screening Assays, Antitumor; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D024505:Tocopherols; D014465:Ultrasonics; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000511:alpha-Macroglobulins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D004304:Dosage Forms; D006360:Heat-Shock Proteins; D000511:alpha-Macroglobulins; D014810:Vitamin E; D024505:Tocopherols