Clinical trials of WT1 peptide vaccine to gynecologic malignancies that are resistant to conventional therapies.

Abstract

5081 Background: Wilms' tumor gene WT1, which has an oncogenic function, is expressed in various kinds of hematological malignancies and solid cancers. The WT1 protein is highly immunogenic and is considered to be a promising target of cancer treatment. On the clinical trials of WT1 peptide vaccine, the decrease of leukemic cells, shrinkage of solid tumor and long-term dormancy of malignancies are reported. We intend to report the clinical trials of WT1 peptide vaccine to gynecologic malignancies which are resistant to conventional therapies. Methods: Twenty one cases of gynecologic malignancy (12 cases of ovarian cancer, 4 of cervical cancer, 1 of endometrial cancer and 4 cases of other malignant tumor), which are resistant to first-/second-line therapy, were included to the trial. After obtainment of informed consent, modified WT1235 type peptide is injected intracutaneously to the HLA-A*2402- positive patients, whose tumor tissues expressed WT1 protein. The injection was repeated weekly to total of 12 times. Immune response to WT1 peptide was monitored with delayed type hypersensitivity (DTH). Side effect due tothe injection was also monitored. The antitumor effect was assessed based on Response Evaluation Criteria in Solid Tumors (RECIST). If any clinical effect is observed, the injection of the vaccine was continued biweekly. Results: In 15 (71%) of 21 patients, the 12 times of injection are completed. In remaining 6 cases, injection had been stopped due to worsening of performance status. Only 1 patient showed grade 3 vesicle at the injection site, however, no patient was cancelled the injection due to severe side effect. The SD status in RECIST criteria is observed in 5 (24%) patients and the injection is continued for these 5 patients, with the maximum of 29 times. Patients who is positive to DTH reaction during therapy, showed significantly longer overall survival than patients who are negative to DTH through the treatment. Conclusions: It was considered that the induction of WT1-specific immunological responses contributed to the occurrence of clinical responses. Some patients reached long-term dormancy of the tumor. We recognized the WT1 peptide vaccine is a new strategy for gynecologic malignancies. No significant financial relationships to disclose.