A Pilot Trial of Tumor Lysate-Loaded Dendritic Cells for the Treatment of Metastatic Renal Cell Carcinoma
Autor: | Allan J. Pantuck, Debby H. Chao, Cho-Lea Tso, Arie S. Belldegrun, Andreas Hinkel, Peter F.A. Mulders, Amnon Zisman, Robert A. Figlin, Barbara J. Gitlitz, Nancy Moldawer |
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Rok vydání: | 2003 |
Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty CD14 medicine.medical_treatment Immunology Pilot Projects Cancer Vaccines Nephrectomy Polymerase Chain Reaction Immunophenotyping Immune system Renal cell carcinoma In vivo Internal medicine Tumor Cells Cultured medicine Humans Immunology and Allergy Carcinoma Renal Cell Cells Cultured Aged Pharmacology Performance status business.industry Vaccination Dendritic Cells Dendritic cell Middle Aged medicine.disease Kidney Neoplasms Treatment Outcome Cytokines Female business |
Zdroj: | Journal of Immunotherapy. 26:412-419 |
ISSN: | 1524-9557 |
DOI: | 10.1097/00002371-200309000-00004 |
Popis: | 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. |
Databáze: | OpenAIRE |
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