A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma

<p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it&...

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Bibliographic Details
Main Authors: Steinberg Seth M, Linehan W Marston, Herrin Vincent E, Gause Barry, Toubaji Antoun, Ibrahim Ramy, Ashtar Ed, Rahma Osama E, Grollman Frank, Grimes George, Bernstein Sarah A, Berzofsky Jay A, Khleif Samir N
Format: Article
Language:English
Published: BMC 2010-01-01
Series:Journal of Translational Medicine
Online Access:http://www.translational-medicine.com/content/8/1/8
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Summary:<p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it>) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.</p> <p>Methods</p> <p>Six patients with advanced RCC and mutated <it>VHL </it>genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock.</p> <p>Results</p> <p>Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively.</p> <p>Conclusions</p> <p>The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials. Trial registration: 98C0139</p>
ISSN:1479-5876