Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

Kyogoku, Noriaki; Ikeda, Hiroaki; Tsuchikawa, Takahiro et al.

Oncology Letters, 2016, 12(6), 4493-4504

Permalink : https://hdl.handle.net/2115/64709

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アクセス権
open access
URI
https://hdl.handle.net/2115/64709
タイトル
Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel
著者
Kyogoku, Noriaki ; Ikeda, Hiroaki ; Tsuchikawa, Takahiro ; Abiko, Takehiro ; Fujiwara, Aki ; Maki, Takehiro ; Yamamura, Yoshiyuki ; Ichinokawa, Masaomi ; Tanaka, Kimitaka ; Imai, Naoko ; Miyahara, Yoshihiro ; Kageyama, Shinichi ; Shiku, Hiroshi ; Hirano, Satoshi
著者名
Kyogoku, Noriaki
e-Rad_Researcher
40374673
著者名
Ikeda, Hiroaki
e-Rad_Researcher
50507572
著者名
Tsuchikawa, Takahiro
著者名
Abiko, Takehiro
著者名
Fujiwara, Aki
著者名
Maki, Takehiro
著者名
Yamamura, Yoshiyuki
著者名
Ichinokawa, Masaomi
e-Rad_Researcher
10758642
著者名
Tanaka, Kimitaka
e-Rad_Researcher
30550975
著者名
Imai, Naoko
e-Rad_Researcher
10582083
著者名
Miyahara, Yoshihiro
e-Rad_Researcher
80194695
著者名
Kageyama, Shinichi
e-Rad_Researcher
80154194
著者名
Shiku, Hiroshi
e-Rad_Researcher
50322813
著者名
Hirano, Satoshi
言語
英語
キーワード
immunoglobulin E
MAGE-A4
vaccine
antibody response
immunoglobulin G subclass
発行日
2016-12
出版者
Spandidos Publications
収録物名
Oncology Letters
巻(号)
12(6)
ページ
4493-4504
抄録
A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 μg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 μg and 3 patients with 300 μg CHP-MAGE-A4, and 3 patients with 300 μg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
PISSN
1792-1074
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.3892/ol.2016.5253