WT1 PEPTIDE-BASED CANCER IMMUNOTHERAPY

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Abstract

In 2001, a phase I clinical study of cancer immunotherapy targeting the WT1 protein was carried out for the first time for patients with leukemia, MDS, lung cancer, or breast cancer. Patients were intradermally injected with an HLA-A*2402-restricted, natural (CMTWNQMNL) or modified (CYTWNQMNL) 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses. Toxicity consisted only of local erythema at the WT1 vaccine injection sites. Four of eight patients with AML who had minimal residual disease for the assessment of clinical effect responded to three injections of WT1 vaccine in decrease in WT1 mRNA levels in peripheral blood. Three of the four patients are successively being injected WT1 vaccine and are in complete remission over 8 years. A new phase I/II clinical study, in which WT1 vaccination was intensified and repeated every week at a dose of 3.0 mg/body of modified WT1 peptide for three months, were started from 2004, and safety of this study was confirmed. Clinical effect of WT1 vaccination is satisfactory for glioblastoma multiforme with relapse and disease control rate is 47.7%. Five of 28 SD (stable disease) patients are long-term survivers and PFS for the four patients in 364, 312, 189, and 158 weeks, respectively. Adverse effect is only erythema at WT1 vaccine injection sites. WT1 vaccination in combination with gemcitabine for 32 patients with advanced pancreatic cancer resulted in 7 PR (21.9%), 17 SD (53.1%), 7PD (21.9%) and 1 unevaluable. Response rate and disease control rate were 21.9% and 75.0%, respectively. Two patients with PR became operable and operation was carried out. Residual tumor masses were completely resected and pathologically examined. No and minimal residual tumor cells were individually observed. Long-term survival and DTH-positivity to WT1 peptide were correlated both in glioblastoma multiforme and advanced pancreatic cancer. Randomized controlled study has been performing for advanced pancreatic cancer.

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