Phase I Clinical Study of Survivin-Derived Peptide Vaccine for Patients with Advanced Gastrointestinal Cancers

Survivin is a member of the Inhibitor of Apoptosis Protein (IAP) family. It is expressed in fetal tissues but not in normal adult tissues. Since Survivin is over expressed in various types of tumor tissues as well as tumor cell lines, it is considered to be suitable as a target antigen for cancer vaccine therapy. We identified an HLA-A24-restricted antigenic peptide, SVN-2B (AYACNTSTL), derived from a splicing variant of Survivin-2B. In the present study, we carried out a phase I clinical study assessing the safety and efficacy of vaccination with the peptide in patients having advanced gastrointestinal cancer. Vaccinations with 0.1mg, 1.0mg, or 3.0mg doses of the SVN-2B peptide were given subcutaneously four times at 14-day intervals. In 20 patients who received at least one vaccination, grade 1 and grade 2 treatment-related adverse events were observed, including injection site extravasation (grade 2), injection site reaction (grade 1), skin induration (grade 1) and fever (grade 1). No severe adverse event was observed in any patient. Based on tumor size evaluated by computed tomography, eight of the 15 patients who completed the vaccination schedule were considered to have stable disease as assessed by the RECIST criteria. Analysis of peripheral blood lymphocytes using HLA-A24/ peptide tetramers revealed the highest increase of SVN-2B-specific cytotoxic T lymphocyte frequency in the 1.0mg dose group. The present clinical study indicates that SVN-2B peptide vaccination is safe and can be considered a potent immunotherapy for HLA-A24positive gastrointestinal cancer patients.