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

Abstract

BackgroundDue 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.MethodsSix 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.ResultsFour 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.ConclusionsThe 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

Induction of HLA-A*33-restricted cytotoxic lymphocytes against renal cell carcinoma targeting galectin 9 and PINCH

“…The cells were subsequently labeled with APC-conjugated anti-CD8 antibody, washed and analyzed using a BD LSR II flow cytometer (BD Sciences). 9 and PINCH in cancer cell lines. Galectin 9 was expressed in the renal cancer cell lines, TUHR-14TKB and VMRC-RCW, and the pancreas cancer cell line, PK-45P.…”

Vaccine-Based Immunotherapy and Targeting the Tumor Microenvironment in Renal Cell Carcinoma

“…In RCC, much attention has been given to vaccination with synthetic peptides to CAIX, a cell surface molecule overexpressed in approximately 90% of RCC [ 23 ] . Also, an exploratory trial investigated the use of a mutant von Hippel-Lindau (VHL) peptide for active immunotherapy and provided evidence for drug safety and immunogenicity against the peptide epitope in the majority of patients studied [ 24 ] .…”

Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

“…For example, T cells specific for unique antigens have been identified in clinically responding melanoma patients treated with adoptively transferred T cells [33]. Similarly, patients with metastatic renal cell carcinoma developed specific T cells to mutated peptides encoded by the von Hippel-Lindau (VHL) gene after peptide vaccination [49]. Somatic mutations in VHL have been observed in over 60% of patients with sporadic renal cell carcinoma.…”