論文

査読有り
2015年4月

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

ONCOLOGY REPORTS
  • Kei Fujio
  • ,
  • Masami Watanabe
  • ,
  • Hideo Ueki
  • ,
  • Shun-Ai Li
  • ,
  • Rie Kinoshita
  • ,
  • Kazuhiko Ochiai
  • ,
  • Junichiro Futami
  • ,
  • Toyohiko Watanabe
  • ,
  • Yasutomo Nasu
  • ,
  • Hiromi Kumon

33
4
開始ページ
1585
終了ページ
1592
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3892/or.2015.3770
出版者・発行元
SPANDIDOS PUBL LTD

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.

リンク情報
DOI
https://doi.org/10.3892/or.2015.3770
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25632844
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000350781400003&DestApp=WOS_CPL
ID情報
  • DOI : 10.3892/or.2015.3770
  • ISSN : 1021-335X
  • eISSN : 1791-2431
  • PubMed ID : 25632844
  • Web of Science ID : WOS:000350781400003

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