A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma.
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.
Gitlitz
Barbara J
BJ
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
Belldegrun
Arie S
AS
Zisman
Amnon
A
Chao
Debby H
DH
Pantuck
Allan J
AJ
Hinkel
Andreas
A
Mulders
Peter
P
Moldawer
Nancy
N
Tso
Cho-Lea
CL
Figlin
Robert A
RA
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
D019496:Cancer Vaccines; D016207:Cytokines