Therapeutic Dendritic Cell Vaccination of Patients With Metastatic Renal Cell Carcinoma : A Clinical Phase 1/2 trial

• Published in: Journal of immunotherapy (1997) Vol. 31; no. 8; pp. 771 - 780
• Main Authors: BERNTSEN, Annika, TREPIAKAS, Redas, SVANE, Inge Marie, WENANDY, Lynn, GEERTSEN, Poul F, THOR STRATEN, Per, ANDERSEN, Mads H, PEDERSEN, Anders E, CLAESSON, Mogens H, LORENTZEN, Torben, JOHANSEN, Julia S
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01-10-2008; Philadelphia,PA
• Subjects: Adipokines; Adult; Aged; Amino Acid Sequence; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - therapeutic use; Carcinoma, Renal Cell - secondary; Carcinoma, Renal Cell - therapy; Cell Line, Tumor; Chitinase-3-Like Protein 1; Dendritic Cells - immunology; Dendritic Cells - transplantation; Female; Glycoproteins - blood; Humans; Immunotherapy; Immunotherapy, Adoptive; Inhibitor of Apoptosis Proteins; Interleukin-2 - immunology; Interleukin-2 - therapeutic use; Interleukin-6 - blood; Kaplan-Meier Estimate; Kidney Neoplasms - pathology; Kidney Neoplasms - therapy; Kidneys; Lectins; Male; Medical sciences; Microtubule-Associated Proteins - immunology; Middle Aged; Molecular Sequence Data; Nephrology. Urinary tract diseases; Peptides - immunology; Pharmacology. Drug treatments; T-Lymphocytes, Cytotoxic - immunology; Telomerase - immunology; Tumors of the urinary system; Vaccination; Carcinoma; Vaccination; Metastasis; YKL-40; Interleukin 6; Prevention; Antigen presenting cell; Immunotherapy; Phase II trial; Secretory protein; Grawitz tumor; Advanced stage; Kidney disease; Human; Dendritic cell; YKL40 protein; Urinary system disease; Cytokine; Malignant tumor; IL-6; cancer vaccination; renal cell carcinoma; Treatment; Kidney cancer; Phase I trial; Cancer
• ISSN: 1524-9557; 1537-4513
• DOI: 10.1097/CJI.0b013e3181833818

Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients obtained disease stabilization (SD) for more than 8 weeks. An antigen-specific immune response was demonstrated in 6/6 patients tested. Furthermore, significant alterations in serum YKL-40 and IL-6 were found during treatment. In conclusion, DC vaccination in our setting is feasible and without severe toxicity. Almost half of the patients obtained SD, and in more than 1/3 of the patients, SD persisted for more than 6 months. However, the evaluation of SD is difficult to interpret in the absence of a randomized trial and, therefore, these results should be interpreted with caution. Antigen-specific immune responses were observed in a subset of the treated patients.