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

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Title: Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel
Authors: Kyogoku, Noriaki Browse this author
Ikeda, Hiroaki Browse this author →KAKEN DB
Tsuchikawa, Takahiro Browse this author →KAKEN DB
Abiko, Takehiro Browse this author
Fujiwara, Aki Browse this author
Maki, Takehiro Browse this author
Yamamura, Yoshiyuki Browse this author
Ichinokawa, Masaomi Browse this author
Tanaka, Kimitaka Browse this author →KAKEN DB
Imai, Naoko Browse this author →KAKEN DB
Miyahara, Yoshihiro Browse this author →KAKEN DB
Kageyama, Shinichi Browse this author →KAKEN DB
Shiku, Hiroshi Browse this author →KAKEN DB
Hirano, Satoshi Browse this author →KAKEN DB
Keywords: immunoglobulin E
MAGE-A4
vaccine
antibody response
immunoglobulin G subclass
Issue Date: Dec-2016
Publisher: Spandidos Publications
Journal Title: Oncology Letters
Volume: 12
Issue: 6
Start Page: 4493
End Page: 4504
Publisher DOI: 10.3892/ol.2016.5253
Abstract: 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.
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article
URI: http://hdl.handle.net/2115/64709
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 京極 典憲

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