Phase I trial of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients.

The aim of this clinical trial was to investigate the toxicity and immunological responses of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients. Patients were confirmed to be human leukocyte antigen (HLA)-A24 or HLA-A2 positive and had histologically confirmed renal cell carcinoma. Ten patients were enrolled in the present study. The peptides to be administered were determined based on the presence of peptide-specific cytotoxic T lymphocyte precursors in peripheral blood mononuclear cells (PBMC) and peptide-specific IgG in the plasma of cancer patients. Patients received subcutaneous injections of four different peptides (3 mg/peptide) every 2 weeks. Vaccinations were well tolerated without any major adverse events. A minimal increase in peptide-specific interferon-gamma production in postvaccination PBMC was observed, regardless of higher levels of cytotoxic T lymphocyte activity in prevaccination PBMC. In contrast, an increase in peptide-specific IgG levels of postvaccination (sixth) plasma was observed in the majority of patients. After progression, five patients received interleukin-2 therapy and continuous vaccination, with survival of 31, 25, 23, 17, and 15 months, but interleukin-2 did not impede humoral responses boosted by the vaccination. These results encourage further clinical trials of personalized peptide vaccinations.

[A phase I study of combination-therapy using personalized peptide vaccine and UFT/UZEL for advanced or recurrent colorectal cancer].

We herein administered combination-therapy using a personalized vaccination and the oral administration of UFT/UZEL for the treatment of either advanced or recurrent colorectal cancer. Safety and the efficacy of this new treatment modality were evaluated. Eight patients were enrolled in this clinical trial from July 2005 to May 2006. Up to 4 kinds of peptide vaccines which were selected according to the immune response of each patient were injected hypodermically every week. At the same time, UFT (300 mg/m2/day) and UZEL (75 mg/day) were also administered orally for 28 days followed by a 7-day rest period. Regarding the adverse events, callosity, a type of leukopenia, and liver-dysfunction, such as hyperbilirubinemia, an increase in the aminotransferase were observed. During the clinical evaluation after the end of the 2 courses, 3 cases showed progressive disease (PD) while 5 cases showed stable disease (SD). Our findings indicate that additional peptide vaccine therapy with UFT/UZEL, can be administered without compromising the patient's safety. Moreover, the use of UFT/UZEL does not normally interfere with the normal course of immune-therapy.