title: A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma.
abstract: Cultured tumor lysate-loaded dendritic cells (TuLy-DC) have been demonstrated in vitro to stimulate potent immune modulations and generate significant antitumor response. We report the results of a pilot trial of TuLy-DC vaccine for patients with metastatic renal cell carcinoma (mRCC). Fourteen mRCC patients underwent nephrectomy to obtain autologous TuLy prepared by subjecting tumor cells to 3 freeze/thaw cycles. Dendritic cells were generated from peripheral blood CD14+ precursors cultured in the presence of GM-CSF, IL-4, and 10% autologous serum. Patients received one vaccination of TuLy alone as an immunologic control, followed by 3 weekly vaccinations of DC-TuLy injected intradermally in the midaxillary region. Peripheral blood lymphocytes were collected before and after weekly vaccines and were assessed for changes in phenotype, cytotoxicity, and cytokine profile. The TuLy-DC vaccine was successfully prepared and administered to 12 patients, whereas 2 patients did not receive vaccine treatment due to declines in postoperative performance status. The vaccines were well tolerated, with only grade 1 toxicities noted. One patient had a partial response to treatment that did not correspond to any significant change in immunologic profile. This pilot trial demonstrated both the safety and feasibility of reliably preparing a DC-based vaccine for mRCC patients. Our data suggest that autologous TuLy-DC vaccines generate only limited clinical response. Further clinical studies are needed to identify the most potent treatment regimen that can consistently mediate an antitumor immune response in vivo.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles, 10945 Le Conte Avenue, Suite 2333, Los Angeles, CA 90095, USA. bgitlitz@mednet.ucla.edu
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Gitlitz
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
authors.forename: Amnon
authors.initials: A
authors.lastname: Zisman
authors.forename: Debby H
authors.initials: DH
authors.lastname: Chao
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
authors.forename: Andreas
authors.initials: A
authors.lastname: Hinkel
authors.forename: Peter
authors.initials: P
authors.lastname: Mulders
authors.forename: Nancy
authors.initials: N
authors.lastname: Moldawer
authors.forename: Cho-Lea
authors.initials: CL
authors.lastname: Tso
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines