| 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)
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