Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

Annika Berntsen, Redas Trepiakas, Lynn Wenandy, Poul F Geertsen, Per thor Straten, Mads H Andersen, Anders E Pedersen, Mogens H Claesson, Torben Lorentzen, Julia S Johansen, Inge Marie Svane

Abstract

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.

OriginalsprogEngelsk
TidsskriftJournal of immunotherapy (Hagerstown, Md. : 1997)
Vol/bind31
Udgave nummer8
Sider (fra-til)771-80
Antal sider10
ISSN1524-9557
DOI
StatusUdgivet - okt. 2008

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