title: Phase II trial of dendritic cells loaded with antigens from self-renewing, proliferating autologous tumor cells as patient-specific antitumor vaccines in patients with metastatic melanoma: final report.
abstract: Between January 2001 and September 2007, we treated 54 metastatic melanoma patients with patient-specific tumor cell vaccines consisting of dendritic cells (DCS), derived from their peripheral blood cells that were cultured in interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor (GM-CSF), which had phagocytosed irradiated autologous tumor cells from a continuously proliferating, self-renewing, autologus tumor cell (TC) culture. The loaded DCs were injected subcutaneously in 500 microg of GM-CSF weekly x three, and then monthly for 5 months, for a total of up to 8 injections. The 34 men and 20 women had a median age of 50.5 years; 32 had M1c (visceral metastases and/or elevated lactate dehydrogenase) as their most advanced disease stage. Overall, 83% had received other systemic therapies, including interferon-alpha (n = 20), biochemotherapy (n = 19), GM-CSF (n = 19), chemotherapy (n = 16), IL-2 (n = 13), and other investigational vaccines (n = 7). Patients received an average of 7.4 vaccinations. Treatment was well-tolerated, with most patients experiencing only mild local pruritus and/or erythema. A positive delayed-type hypersensitivity reaction to purified autologous tumor cells was observed at baseline in only 1 of 54 patients, compared to 12 of 54 following vaccination (p = 0.001). The projected 5-year survival rate is an impressive 54% at a median follow-up of 4.5 years (range, 2.4-7.4) for the 30 surviving patients. This survival was superior to that observed following vaccination with irradiated TC in 48 melanoma patients in a previous trial (64 versus 31 months, p = 0.016). This patient-specific vaccine warrants further investigation, based on its safety and encouraging survival rates. (
  
  
  BACKGROUND
  NCI-V01-1646).
authors.affiliation: Hoag Cancer Center, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
authors.forename: Robert O
authors.initials: RO
authors.lastname: Dillman
authors.forename: Senthamil R
authors.initials: SR
authors.lastname: Selvan
authors.forename: Patric M
authors.initials: PM
authors.lastname: Schiltz
authors.forename: Edward F
authors.initials: EF
authors.lastname: McClay
authors.forename: Neil M
authors.initials: NM
authors.lastname: Barth
authors.forename: Carol
authors.initials: C
authors.lastname: DePriest
authors.forename: Cristina
authors.initials: C
authors.lastname: de Leon
authors.forename: Cheryl
authors.initials: C
authors.lastname: Mayorga
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Cornforth
authors.forename: Kanoe
authors.initials: K
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D001324:Autoantigens / Q000276:immunology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D018450:Disease Progression; D005260:Female; D005732:Gangliosides / Q000097:blood / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010587:Phagocytosis / Q000276:immunology; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001324:Autoantigens; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D016207:Cytokines; D005732:Gangliosides; D007371:Interferon-gamma