Open Access

A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment

  • Authors:
    • Kei Fujio
    • Masami Watanabe
    • Hideo Ueki
    • Shun-Ai Li
    • Rie  Kinoshita
    • Kazuhiko  Ochiai
    • Junichiro  Futami
    • Toyohiko Watanabe
    • Yasutomo Nasu
    • Hiromi Kumon
  • View Affiliations

  • Published online on: January 29, 2015     https://doi.org/10.3892/or.2015.3770
  • Pages: 1585-1592
  • Copyright: © Fujio et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Immunotherapy is one of the attractive treatment strategies for advanced prostate cancer. The US Food and Drug Administration (FDA) previously approved the therapeutic vaccine, sipuleucel-T, which is composed of autologous antigen-presenting cells cultured with a fusion protein [prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF)]. Although sipuleucel-T has been shown to prolong the median survival of patients for 4.1 months, more robust therapeutic effects may be expected by modifying the vaccination protocol. In the present study, we aimed to develop and validate a novel vaccination strategy using multiple PAP-fused cytokines for prostate cancer treatment. Using a super gene expression (SGE) system that we previously established to amplify the production of a recombinant protein, significant amounts of PAP-fused cytokines [human GMCSF, interleukin-2 (IL2), IL4, IL7 and mouse GMCSF and IL4] were obtained. We examined the activity of the fusion proteins in vitro to validate their cytokine functions. A significant upregulation of dendritic cell differentiation from monocytes was achieved by PAP-GMCSF when used with the other PAP-fused cytokines. The PAP-fused human IL2 significantly increased the proliferation of lymphocytes, as determined by flow cytometry. We also investigated the in vivo therapeutic effects of multiple PAP-fused cytokines in a mouse prostate cancer model bearing prostate-specific antigen (PSA)- and PAP-expressing tumors. The simultaneous intraperitoneal administration of PAP-GMCSF, -IL2, -IL4 and -IL7 significantly prevented tumor induction and inhibited the tumor growth in the PAP-expressing tumors, yet not in the PSA-expressing tumors. The in vivo therapeutic effects with the multiple PAP-fused cytokines were superior to the effects of PAP-GMCSF alone. We thus demonstrated the advantages of the combined use of multiple PAP-fused cytokines including PAP-GMCSF, and propose a promising prostatic antigen-vaccination strategy to enhance the therapeutic effects.
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April-2015
Volume 33 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Fujio K, Watanabe M, Ueki H, Li S, Kinoshita R, Ochiai K, Futami J, Watanabe T, Nasu Y, Kumon H, Kumon H, et al: A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment. Oncol Rep 33: 1585-1592, 2015.
APA
Fujio, K., Watanabe, M., Ueki, H., Li, S., Kinoshita, R., Ochiai, K. ... Kumon, H. (2015). A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment. Oncology Reports, 33, 1585-1592. https://doi.org/10.3892/or.2015.3770
MLA
Fujio, K., Watanabe, M., Ueki, H., Li, S., Kinoshita, R., Ochiai, K., Futami, J., Watanabe, T., Nasu, Y., Kumon, H."A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment". Oncology Reports 33.4 (2015): 1585-1592.
Chicago
Fujio, K., Watanabe, M., Ueki, H., Li, S., Kinoshita, R., Ochiai, K., Futami, J., Watanabe, T., Nasu, Y., Kumon, H."A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment". Oncology Reports 33, no. 4 (2015): 1585-1592. https://doi.org/10.3892/or.2015.3770