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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 1 2015

Fingerprint

Wilms Tumor
Glioma
Immunotherapy
Dendritic Cells
Vaccination
Cell- and Tissue-Based Therapy
Neoplasms
Vaccines
Picibanil
Safety
Oligodendroglioma
Peptides
Injections
Astrocytoma
Neoplasm Antigens
Erythema
Glioblastoma
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Sakai, K., Shimodaira, S., Maejima, S., Udagawa, N., Sano, K., Higuchi, Y., ... 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

Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma. / Sakai, Keiichi; Shimodaira, Shigetaka; Maejima, Shinya; Udagawa, Nobuyuki; Sano, Kenji; Higuchi, Yumiko; Koya, Terutsugu; Ochiai, Takanaga; Koide, Masanori; Uehara, Shunsuke; Nakamura, Midori; Sugiyama, Haruo; Yonemitsu, Yoshikazu; Okamoto, Masato; Hongo, Kazuhiro.

In: Journal of Neurosurgery, Vol. 123, No. 4, 01.10.2015, p. 989-997.

Research output: Contribution to journalArticle

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, vol. 123, no. 4, pp. 989-997. https://doi.org/10.3171/2015.1.JNS141554
Sakai, Keiichi ; Shimodaira, Shigetaka ; Maejima, Shinya ; Udagawa, Nobuyuki ; Sano, Kenji ; Higuchi, Yumiko ; Koya, Terutsugu ; Ochiai, Takanaga ; Koide, Masanori ; Uehara, Shunsuke ; Nakamura, Midori ; Sugiyama, Haruo ; Yonemitsu, Yoshikazu ; Okamoto, Masato ; Hongo, Kazuhiro. / Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma. In: Journal of Neurosurgery. 2015 ; Vol. 123, No. 4. pp. 989-997.
@article{73ea85cff06e44049994530b7a067ebd,
title = "Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma",
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.",
author = "Keiichi Sakai and Shigetaka Shimodaira and Shinya Maejima and Nobuyuki Udagawa and Kenji Sano and Yumiko Higuchi and Terutsugu Koya and Takanaga Ochiai and Masanori Koide and Shunsuke Uehara and Midori Nakamura and Haruo Sugiyama and Yoshikazu Yonemitsu and Masato Okamoto and Kazuhiro Hongo",
year = "2015",
month = "10",
day = "1",
doi = "10.3171/2015.1.JNS141554",
language = "English",
volume = "123",
pages = "989--997",
journal = "Journal of Neurosurgery",
issn = "0022-3085",
publisher = "American Association of Neurological Surgeons",
number = "4",

}

TY - JOUR

T1 - Dendritic cell-based immunotherapy targeting Wilms' tumor 1 in patients with recurrent malignant glioma

AU - Sakai, Keiichi

AU - Shimodaira, Shigetaka

AU - Maejima, Shinya

AU - Udagawa, Nobuyuki

AU - Sano, Kenji

AU - Higuchi, Yumiko

AU - Koya, Terutsugu

AU - Ochiai, Takanaga

AU - Koide, Masanori

AU - Uehara, Shunsuke

AU - Nakamura, Midori

AU - Sugiyama, Haruo

AU - Yonemitsu, Yoshikazu

AU - Okamoto, Masato

AU - Hongo, Kazuhiro

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84953344525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953344525&partnerID=8YFLogxK

U2 - 10.3171/2015.1.JNS141554

DO - 10.3171/2015.1.JNS141554

M3 - Article

VL - 123

SP - 989

EP - 997

JO - Journal of Neurosurgery

JF - Journal of Neurosurgery

SN - 0022-3085

IS - 4

ER -