Phase I clinical trial of a novel peptide vaccine in combination with UFT/LV for metastatic colorectal cancer.

To test the safety and immune responses of a novel peptide vaccine derived from RNF43 (ring finger protein 43) and TOMM34 (34-kDa translocase of the outer mitochondrial membrane) administered in combination with chemotherapy in patients with metastatic colorectal cancer, a phase I clinical trial with 21 HLA-A2402-positive metastatic colorectal cancer patients was conducted. Patients received a weekly peptide vaccine (1 mg of each peptide in incomplete Freund's adjuvant) in combination with oral UFT (300 mg/m(2)/day) and UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. The protocol consisted of at least two cycles of this regimen. After the 2nd cycle, vaccinations were given biweekly or monthly, depending on the condition of the patient. Clinical responses were judged 10 weeks after the 2nd cycle by performing computed tomography (CT) scans and assessing the cytotoxic T lymphocyte (CTL) responses against RNF43 and TOMM34 in peripheral lymphocytes. The vaccinations were well tolerated without any serious adverse events. CTL responses were induced against both antigens in 8 patients and against one antigen in 12 patients, while 1 patient had no CTL response. The rate of stable disease was 83%. The group with CTL responses against both antigens had the most long-term survivors, followed by the group showing CTL responses against one antigen (p=0.0079). The patients with no CTL responses had the lowest survival. The safety and immunological responsiveness of the present combination therapy suggests that it is clinically beneficial for metastatic colorectal cancer. Further clinical trials are warranted.