Abstract
10042 Background: WT1 (Wilms’ tumor gene) is originally isolated as a tumor-suppressor gene in a subset of Wilms’ tumors, however, recent studies have indicated its oncogenic activity in various types of cancers, and demonstrated that WT1-specific cytotoxic T lymphocytes specifically kill WT1-expressing cancer cells, thus WT1 protein can be a molecular target for cancer immunotherapy as an attractive tumor rejection antigen. However, WT1 expression in human bone and soft-tissue sarcomas has been poorly understood. Methods: 1) The expression levels of WT1 gene were examined in 36 cases of various types of human bone and soft-tissue sarcomas using quantitative RT-PCR method. They included 12 MFH (11 soft-tissue, 1 bone), 9 osteosarcomas, 6 synovial sarcomas, 4 myxoid liposarcomas, 3 MPNST, one each case of angiosarcoma and clear cell sarcoma. 2) Then, we conducted a phase I/II clinical trial of tumor-specific immunotherapy targeting WT1 peptide for various kinds of cancers including 12 patients with locally advanced and/or metastatic sarcoma (bone 2, soft-tissue 10) which showed WT1 expression and HLA -A*2402. Patients were intracutaneously injected with 3.0mg of HLA- A*2402-restricted natural/or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant weekly. After 12-times injection, clinical response was evaluated by RECIST. Results: 1) 28 (78%) out of 36 cases of various types of bone and soft-tissue sarcomas overexpressed the WT1 gene, and its expression at the protein level was confirmed by immunohistochemical analysis, suggesting a possibility of immunotherapy using WT1 peptide vaccine for sarcomas. 2) The clinical responses included 4 SD and 7 PD with a case of long-standing SD over 1.5 years. One patient discontinued treatment with patient's decision. There were no patients with objective response (PR/CR). Conclusion: The present preliminary study suggested that tumor immunotherapy using WT1 peptide vaccine can be a new treatment strategy for patients with bone and soft-tissue sarcomas. No significant financial relationships to disclose.
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