A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carci
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RESEARCH
Open Access
A pilot clinical trial testing mutant von HippelLindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma Osama E Rahma1, Ed Ashtar1, Ramy Ibrahim1, Antoun Toubaji1, Barry Gause2, Vincent E Herrin3, W Marston Linehan4, Seth M Steinberg5, Frank Grollman1, George Grimes6, Sarah A Bernstein2, Jay A Berzofsky1, Samir N Khleif1,3*
Abstract Background: 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 von Hippel-Lindau (VHL) 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. Methods: Six patients with advanced RCC and mutated VHL 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. Results: 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. Conclusions: 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
Background Renal cell carcinoma comprises the majority of malignant kidney tumors. It is relatively rare in the United States but its incidence has continued to rise since 1975 [1,2]. The lifetime risk of developing RCC is 1 in 11,000 [3]. Earlier detection and treatment of smaller renal tumors has not significantly reduced the mortality rate and about one-third of patients still present with metastatic disease [4]. Indeed, the mortality rate has continued to rise, which necessitates looking for a better therapeutic strategy [5,6]. RCC is one of the most resistant forms of cancers to both radiation and chemotherapy. Recently, the multitargeted tyrosine kinase inhibitors Sorafenib and * Correspondence: [email protected] 1 Vaccine Branch, NCI, NIH, Bethesda, MD, USA
Sunitinib have shown 10% and 34-44% objective response rates, respectively, in metastatic RCC [7-9]. Accordingly, we are still in need of novel and successful therapeutic approaches to RCC. Clear cell renal carcinoma (CCRC) is the most common histological subtype of RCC and accounts for about 70% of cases [10]. This tumor is often regarded as immunogenic based on the obser
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