Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma

Keiichi Sakai, Shigetaka Shimodaira, Shinya Maejima, Nobuyuki Udagawa, Kenji Sano, Yumiko Higuchi, Terutsugu Koya, Takanaga Ochiai, Masanori Koide, Shunsuke Uehara, Midori Nakamura, Haruo Sugiyama, Yoshikazu Yonemitsu, Masato Okamoto, Kazuhiro Hongo

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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 × 107 to 2 × 107 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.

Original languageEnglish
Pages (from-to)989-997
Number of pages9
JournalJournal of Neurosurgery
Volume123
Issue number4
DOIs
Publication statusPublished - Oct 2015

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

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    Sakai, K., Shimodaira, S., Maejima, S., Udagawa, N., Sano, K., Higuchi, Y., Koya, T., Ochiai, T., Koide, M., Uehara, S., Nakamura, M., Sugiyama, H., Yonemitsu, Y., Okamoto, M., & Hongo, K. (2015). Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma. Journal of Neurosurgery, 123(4), 989-997. https://doi.org/10.3171/2015.1.JNS141554