tailieunhanh - Báo cáo hóa học: " A pilot clinical trial testing mutant von HippelLindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma"

A pilot clinical trial testing mutant von HippelLindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma | Rahma et al. Journal of Translational Medicine 2010 8 8 http content 8 1 8 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma 11 1 12 3 Osama E Rahma Ed Ashtar Ramy Ibrahim Antoun Toubaji Barry Gause Vincent E Herrin 4 5 1 6 2 1 Marston Linehan Seth M Steinberg Frank Grollman George Grimes Sarah A Bernstein Jay A Berzofsky 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 and 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. .