Keiichi Sakai1,2, Shigetaka Shimodaira3, Shinya Maejima4, Nobuyuki Udagawa4, Kenji Sano5, Yumiko Higuchi3, Terutsugu Koya3, Takanaga Ochiai6, Masanori Koide7, Shunsuke Uehara8, Midori Nakamura8, Haruo Sugiyama9, Yoshikazu Yonemitsu10, Masato Okamoto11, Kazuhiro Hongo1. 1. Department of Neurosurgery, Shinshu University School of Medicine; 2. Department of Neurosurgery, National Hospital Organization, Shinshu Ueda Medical Center, Ueda, Nagano, Japan. 3. Center for Advanced Cellular Therapy, Shinshu University Hospital, Matsumoto; 4. Dendritic Cell Vaccination Therapy Center. 5. Department of Laboratory, Shinshu University Hospital, Matsumoto; 6. Department of Oral Pathology. 7. Institute for Oral Science, and. 8. Department of Biochemistry, Matsumoto Dental University Hospital, Shiojiri; 9. Department of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Osaka; 10. R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka; 11. Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Minato-ku, Tokyo; and.
Abstract
OBJECT: Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms' tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. METHODS: WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 10(7) to 2 × 10(7) pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5-7 sessions (1 course) during an individual chemotherapy regimen. RESULTS: Ten patients (3 men, 7 women; age range 24-64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide-pulsed DC vaccine was administered to 7 patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate-pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1-2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session. CONCLUSIONS: This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.
OBJECT: Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms' tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. METHODS:WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 10(7) to 2 × 10(7) pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5-7 sessions (1 course) during an individual chemotherapy regimen. RESULTS: Ten patients (3 men, 7 women; age range 24-64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide-pulsed DC vaccine was administered to 7patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate-pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1-2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session. CONCLUSIONS: This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.
Entities:
Keywords:
CTL = cytotoxic T lymphocyte; DC = dendritic cell; HLA = human leukocyte antigen; IL = interleukin; KPS = Karnofsky Performance Scale; Ke = kiloequivalent; MST = median overall survival time; PD = progressive disease; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease; TAA = tumor-associated antigen; WT1; WT1 = Wilms’ tumor 1; dendritic cell; immunotherapy; oncology; relapsed malignant glioma