title: Dendritic Versus Tumor Cell Presentation of Autologous Tumor Antigens for Active Specific Immunotherapy in Metastatic Melanoma: Impact on Long-Term Survival by Extent of Disease at the Time of Treatment.
abstract: In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials. Pooled data confirmed that overall survival (OS) was longer in 72 patients treated with DC-TC compared with 71 patients treated with TC (median OS 60 versus 22 months; 5-year OS 51% versus 32%, p=0.004). Treatment with DC-TC was associated with longer OS in both cohorts. Among 70 patients who were NED at the time that treatment was started, OS was better for DC-TC: 5-year OS 73% versus 43% (p=0.015). Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025). This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma.
authors.affiliation: 1 Caladrius Biosciences, Inc. , Irvine, California.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Dillman
authors.affiliation: 2 California Cancer Associates for Research and Excellence (cCARE) , Institute for Melanoma Research & Education , Encinitas California.
authors.forename: Edward F
authors.initials: EF
authors.lastname: McClay
authors.affiliation: 3 Genomics Institute Inc. , Laguna Beach, California.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Barth
authors.affiliation: 4 Minnesota Oncology , Fridley, Minnesota.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Amatruda
authors.affiliation: 5 The West Clinic , Memphis, Tennessee.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Schwartzberg
authors.affiliation: 6 Newport Doctors Medical Group , Newport Beach, California.
authors.forename: Khosrow
authors.initials: K
authors.lastname: Mahdavi
authors.affiliation: 7 Hoag Institute for Research and Education , Newport Beach, California.
authors.forename: Cristina
authors.initials: C
authors.lastname: de Leon
authors.affiliation: 7 Hoag Institute for Research and Education , Newport Beach, California.
authors.forename: Robin E
authors.initials: RE
authors.lastname: Ellis
authors.affiliation: 8 Cancer Biotherapy Research Group , Franklin, Tennessee.
authors.forename: Carol
authors.initials: C
authors.lastname: DePriest
mesh_terms: D017951:Antigen Presentation; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D058950:Melanoma-Specific Antigens / Q000276:immunology; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000637:transplantation*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D015996:Survival Rate; D047368:Tumor Burden; D014407:Tumor Cells, Cultured / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D058950:Melanoma-Specific Antigens; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: active specific immunotherapy; cancer stem cells; dendritic cells; melanoma; therapeutic cancer vaccines