title: Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide.
abstract: In this phase I/II study, we evaluated the feasibility, safety and efficacy of allogeneic dendritic cells (DCs) with or without cyclophosphamide in the treatment of patients with metastatic renal cell carcinoma (RCC). Immunomagnetic beads were used to isolate CD14(+) monocytes from healthy donor leukapheresis products, and CD83(+) antigen-pulsed monocyte-derived DCs (moDCs) loaded with tumor lysate and keyhole limpet hemocyanin (KLH) were generated. Twelve patients were treated with allogeneic moDCs alone, while ten patients also received cyclophosphamide on days 4 and 3 prior to vaccination. Of the 22 patients enrolled, 20 received full treatment consisting of at least three vaccinations at monthly intervals. Two mixed responses with substantial tumor regression were observed. In 3 patients, disease stabilization occurred, in 13 patients disease progressed and 4 patients were lost to follow-up. Overall, immune responses against KLH and tumor lysate were weak or absent; however, the strongest increases in antigen-independent and KLH-specific responses were observed in the 2 patients with mixed responses. In addition, 1 of them showed a substantial increase in oncofetal antigen (OFA)-specific IFN-gamma production. Importantly, the 2 mixed responders and 1 patient with stable disease belonged to the cyclophosphamide group. Median overall survival in the cyclophosphamide group was 23.2 and 20.3 months in the group that received allogeneic moDCs alone. Allogeneic immunotherapy with moDCs is feasible and well tolerated. However, the immunogenicity of allogeneic moDCs is clearly less pronounced than that of autologous moDC immunotherapy. Cyclophosphamide may have the capacity to augment DC-induced antitumor immunity.
authors.affiliation: Department of Urology/kompetenzzentrum medizin tirol, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Höltl
authors.forename: Reinhold
authors.initials: R
authors.lastname: Ramoner
authors.forename: Claudia
authors.initials: C
authors.lastname: Zelle-Rieser
authors.forename: Hubert
authors.initials: H
authors.lastname: Gander
authors.forename: Thomas
authors.initials: T
authors.lastname: Putz
authors.forename: Christine
authors.initials: C
authors.lastname: Papesh
authors.forename: Walter
authors.initials: W
authors.lastname: Nussbaumer
authors.forename: Claudia
authors.initials: C
authors.lastname: Falkensammer
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Martin
authors.initials: M
authors.lastname: Thurnher
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D006433:Hemocyanins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014611:Vaccination
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; C031192:oncofetal antigens; D007371:Interferon-gamma; D003520:Cyclophosphamide; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin