6 results on '"Udaka K"'
Search Results
2. A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data.
- Author
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Morita S, Oka Y, Tsuboi A, Kawakami M, Maruno M, Izumoto S, Osaki T, Taguchi T, Ueda T, Myoui A, Nishida S, Shirakata T, Ohno S, Oji Y, Aozasa K, Hatazawa J, Udaka K, Yoshikawa H, Yoshimine T, Noguchi S, Kawase I, Nakatsuka S, Sugiyama H, and Sakamoto J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bayes Theorem, Cancer Vaccines adverse effects, Female, Humans, Injections, Intradermal, Male, Middle Aged, Vaccination, WT1 Proteins adverse effects, Breast Neoplasms therapy, Cancer Vaccines therapeutic use, Central Nervous System Neoplasms therapy, Glioblastoma therapy, Immunotherapy, WT1 Proteins therapeutic use
- Abstract
Objective: We conducted a phase I study to investigate the safety of a weekly WT1 tumor vaccine therapy in patients with solid tumors that had been refractory to all other anti-cancer therapies., Methods: Skin-test-negative patients were intradermally injected weekly for 12 weeks with 3.0 mg of an HLA-A*2402-restricted modified 9-mer WT1 peptide emulsified in Montanide ISA51 adjuvant. We estimated the Bayesian posterior probability of the occurrence of grade 3 or 4 toxicity when receiving the weekly WT1 vaccination. This analysis provided the basis for making a decision to terminate the phase I study and switch to phase II. Moreover, we performed an exploratory assessment of the anti-tumor effects of WT1 treatment., Results: Ten patients received 114 vaccinations with WT1 on a weekly schedule. No grade 3 or 4 toxicities were observed. Based on the Bayesian approach, it was highly likely that the probability of grade 3 or 4 toxicity was below 20% (the posterior probability = 0.914). Fifteen grade 2 and two grade 1 toxicities were observed; all of these incidents, however, were determined by the Independent Data and Safety Monitoring Committee to be unrelated to the WT1 treatment. One patient exhibited a partial response; five additional patients had stable disease while receiving weekly WT1 treatment., Conclusion: This paper confirms that the potential toxicities of the treatment schedule of weekly WT1 vaccination are acceptable and suggested a potential anti-tumor effect. Consequently, we validated the decision to continue to the phase II trial.
- Published
- 2006
- Full Text
- View/download PDF
3. Development of WT1 peptide cancer vaccine against hematopoietic malignancies and solid cancers.
- Author
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Oka Y, Tsuboi A, Kawakami M, Elisseeva OA, Nakajima H, Udaka K, Kawase I, Oji Y, and Sugiyama H
- Subjects
- Animals, Clinical Trials as Topic, Disease Models, Animal, Drug Design, Genes, Wilms Tumor, Hematologic Neoplasms therapy, Humans, Mice, Peptides, Cancer Vaccines immunology, Immunotherapy methods, Neoplasms therapy, WT1 Proteins immunology
- Abstract
Wild-type Wilms' tumor gene WT1 is highly expressed not only in hematopoietic malignancies, including leukemia and myelodysplastic syndromes (MDS), but also in various kinds of solid tumors. Human cytotoxic T lymphocytes (CTLs) which could specifically lyse WT1-expressing tumor cells with HLA class I restriction were generated in vitro. We have also demonstrated that mice immunized with the WT1 peptide or WT1 cDNA rejected challenges by WT1-expressing tumor cells and survived with no signs of auto-aggression to normal organs which physiologically expressed WT1 in prophylactic and therapeutic models. Furthermore, we and others detected IgM and IgG WT1 antibodies in the patients with hematopoietic malignancies, indicating that WT1 protein was highly immunogenic, and that immunoglobulin class-switch-inducing WT1-specific cellular immune responses were elicited in the patients. CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients. These results provided us with the rationale for elicitation of CTL responses targeting the WT1 product for cancer immunotherapy. On the basis of the findings mentioned above, we performed a phase I clinical trial of WT1 peptide cancer vaccine for the patients with malignant neoplasms. These results strongly suggested that WT1 peptide cancer vaccine had efficacy in the clinical setting, because clinical responses, including reduction of leukemic blast cells or regression of tumor masses, were observed after the WT1 vaccination in patients with hematopoietic malignancies or solid cancers. The power of TAA-derived cancer vaccine may be enhanced by combination with stronger adjuvants, helper peptide, or conventional treatments such as molecular-target-based drugs.
- Published
- 2006
- Full Text
- View/download PDF
4. WT1 peptide-based immunotherapy for patients with lung cancer: report of two cases.
- Author
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Tsuboi A, Oka Y, Osaki T, Kumagai T, Tachibana I, Hayashi S, Murakami M, Nakajima H, Elisseeva OA, Fei W, Masuda T, Yasukawa M, Oji Y, Kawakami M, Hosen N, Ikegame K, Yoshihara S, Udaka K, Nakatsuka S, Aozasa K, Kawase I, and Sugiyama H
- Subjects
- Aged, Antigens, Neoplasm therapeutic use, Cancer Vaccines adverse effects, Cancer Vaccines therapeutic use, Drug Delivery Systems adverse effects, Drug Delivery Systems methods, Female, HLA-A Antigens administration & dosage, HLA-A Antigens therapeutic use, Humans, Lung Neoplasms etiology, Lung Neoplasms pathology, Male, Middle Aged, Peptide Fragments administration & dosage, Peptide Fragments immunology, Peptide Fragments therapeutic use, Treatment Outcome, WT1 Proteins immunology, WT1 Proteins therapeutic use, Antigens, Neoplasm administration & dosage, Cancer Vaccines genetics, Cancer Vaccines immunology, Immunotherapy methods, Lung Neoplasms therapy, WT1 Proteins administration & dosage
- Abstract
The Wilms' tumor gene WT1 is overexpressed in various types of solid tumors, including lung and breast cancer and WT1 protein is a tumor antigen for these malignancies. In phase I clinical trials of WT1 peptide-based cancer immunotherapy, two patients with advanced lung cancer were intradermally injected with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant. Consecutive WT1 vaccination at 2-week intervals resulted in a reduction in tumor markers such as chorio-embryonic antigen (CEA) and sialyl Lewis (x) (SLX) and by a transient decrease in tumor size. No adverse effects except for local erythema at the injection sites of WT1 vaccine were observed. These results provided us with the first clinical evidence demonstrating that WT1 peptide-based immunotherapy should be a promising treatment for patients with lung cancer.
- Published
- 2004
- Full Text
- View/download PDF
5. Wilms tumor gene peptide-based immunotherapy for patients with overt leukemia from myelodysplastic syndrome (MDS) or MDS with myelofibrosis.
- Author
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Oka Y, Tsuboi A, Murakami M, Hirai M, Tominaga N, Nakajima H, Elisseeva OA, Masuda T, Nakano A, Kawakami M, Oji Y, Ikegame K, Hosen N, Udaka K, Yasukawa M, Ogawa H, Kawase I, and Sugiyama H
- Subjects
- Aged, Antigens, Neoplasm therapeutic use, Female, HLA-A Antigens administration & dosage, HLA-A Antigens therapeutic use, Humans, Leukemia etiology, Leukemia pathology, Male, Middle Aged, Peptide Fragments administration & dosage, Peptide Fragments immunology, Peptide Fragments therapeutic use, Primary Myelofibrosis pathology, Treatment Outcome, Vaccination, Antigens, Neoplasm administration & dosage, Immunotherapy methods, Leukemia therapy, Myelodysplastic Syndromes pathology, WT1 Proteins immunology
- Abstract
The Wilms tumor gene, WT1, is overexpressed not only in leukemias and myelodysplastic syndrome (MDS) but also in various types of solid tumors, including lung and breast cancer, and the WT1 protein is a tumor antigen for these malignancies. In clinical trials of WT1 peptide-based cancer immunotherapy, patients with overt leukemia from MDS or MDS with myelofibrosis were injected intradermally with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant. Only a single dose of WT1 vaccination resulted in an increase in WT1-specific cytotoxic T-lymphocytes, which was followed by a rapid reduction in leukemic blast cells. Severe leukopenia and local erythema at the injection sites of WT1 peptide were observed as adverse effects. These results have provided us with the first clinical evidence suggesting that WT1 peptide-based immunotherapy is an attractive treatment for patients with leukemias or MDS.
- Published
- 2003
- Full Text
- View/download PDF
6. Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1โ) product
- Author
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Oka, Y., Elisseeva, O. A., Tsuboi, A., Ogawa, H., Tamaki, H., Li, H., Oji, Y., Kim, E. H., Soma, T., Asada, M., Ueda, K., Maruya, E., Saji, H., Kishimoto, T., Udaka, K., and Sugiyama, H.
- Published
- 2000
- Full Text
- View/download PDF
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