Open Access

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:
    • Noriaki Kyogoku
    • Hiroaki Ikeda
    • Takahiro Tsuchikawa
    • Takehiro Abiko
    • Aki Fujiwara
    • Takehiro Maki
    • Yoshiyuki Yamamura
    • Masaomi Ichinokawa
    • Kimitaka Tanaka
    • Naoko Imai
    • Yoshihiro Miyahara
    • Shinichi Kageyama
    • Hiroshi Shiku
    • Satoshi Hirano
  • View Affiliations

  • Published online on: October 13, 2016     https://doi.org/10.3892/ol.2016.5253
  • Pages: 4493-4504
  • Copyright: © Kyogoku et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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December-2016
Volume 12 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Kyogoku N, Ikeda H, Tsuchikawa T, Abiko T, Fujiwara A, Maki T, Yamamura Y, Ichinokawa M, Tanaka K, Imai N, Imai N, et al: Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel. Oncol Lett 12: 4493-4504, 2016
APA
Kyogoku, N., Ikeda, H., Tsuchikawa, T., Abiko, T., Fujiwara, A., Maki, T. ... Hirano, S. (2016). Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel. Oncology Letters, 12, 4493-4504. https://doi.org/10.3892/ol.2016.5253
MLA
Kyogoku, N., Ikeda, H., Tsuchikawa, T., Abiko, T., Fujiwara, A., Maki, T., Yamamura, Y., Ichinokawa, M., Tanaka, K., Imai, N., Miyahara, Y., Kageyama, S., Shiku, H., Hirano, S."Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel". Oncology Letters 12.6 (2016): 4493-4504.
Chicago
Kyogoku, N., Ikeda, H., Tsuchikawa, T., Abiko, T., Fujiwara, A., Maki, T., Yamamura, Y., Ichinokawa, M., Tanaka, K., Imai, N., Miyahara, Y., Kageyama, S., Shiku, H., Hirano, S."Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel". Oncology Letters 12, no. 6 (2016): 4493-4504. https://doi.org/10.3892/ol.2016.5253