Combination immunotherapy with 4-1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor

Yoshitaro Shindo, Kiyoshi Yoshimura, Atsuo Kuramasu, Yusaku Watanabe, Hideaki Ito, Tomoko Kondo, Atsunori Oga, Hiroshi Ito, Shigefumi Yoshino, Shoichi Hazama, Koji Tamada, Hideo Yagita, Masaaki Oka

Research output: Contribution to journalArticle

Abstract

Background/Aim: The purpose of the present study was to establish an effective immunotherapy by skewing the cosignal balance to be on the positive side by using the combination of monoclonal antibody (mAb) against 4-1BB also known as Cluster of Differentiation (CD) 137 as a co-stimulatory effector and to programmed death-1 (PD- 1) to blockade the immune checkpoint.

Materials and Methods: Mice implanted with 1×105 CT26 cells were treated with anti 4-1BB mAb alone, anti PD-1 mAb alone, or both anti 4-1BB mAb and anti PD-1 mAb. Immune cell populations were analyzed by flow cytometry. Tumorinfiltrating T-cells were evaluated by immunohistochemistry.

Results: Mice treated with the combination therapy had the best antitumor response that resulted in complete tumor rejection. The numbers of CD4+ interferon (IFN)-γ+ and CD8+ IFN-γ+ T-cells were significantly higher in the combination group. The number of tumor-infiltrating T-cells was significantly increased in the combination therapy.

Conclusion: The therapeutic strategy of targeting co-signal molecules has promising clinical applications in the future.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalAnticancer Research
Volume35
Issue number1
StatePublished - Jan 1 2015
Externally publishedYes

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Immunotherapy
Monoclonal Antibodies
Neoplasms
T-Lymphocytes
Interferons
Flow Cytometry
Therapeutics
Immunohistochemistry
Population

Keywords

  • 4-1BB
  • Cancer immunotherapy
  • Immune checkpoint
  • PD-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Shindo, Y., Yoshimura, K., Kuramasu, A., Watanabe, Y., Ito, H., Kondo, T., ... Oka, M. (2015). Combination immunotherapy with 4-1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor. Anticancer Research, 35(1), 129-136.

Combination immunotherapy with 4-1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor. / Shindo, Yoshitaro; Yoshimura, Kiyoshi; Kuramasu, Atsuo; Watanabe, Yusaku; Ito, Hideaki; Kondo, Tomoko; Oga, Atsunori; Ito, Hiroshi; Yoshino, Shigefumi; Hazama, Shoichi; Tamada, Koji; Yagita, Hideo; Oka, Masaaki.

In: Anticancer Research, Vol. 35, No. 1, 01.01.2015, p. 129-136.

Research output: Contribution to journalArticle

Shindo, Y, Yoshimura, K, Kuramasu, A, Watanabe, Y, Ito, H, Kondo, T, Oga, A, Ito, H, Yoshino, S, Hazama, S, Tamada, K, Yagita, H & Oka, M 2015, 'Combination immunotherapy with 4-1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor', Anticancer Research, vol. 35, no. 1, pp. 129-136.
Shindo, Yoshitaro ; Yoshimura, Kiyoshi ; Kuramasu, Atsuo ; Watanabe, Yusaku ; Ito, Hideaki ; Kondo, Tomoko ; Oga, Atsunori ; Ito, Hiroshi ; Yoshino, Shigefumi ; Hazama, Shoichi ; Tamada, Koji ; Yagita, Hideo ; Oka, Masaaki. / Combination immunotherapy with 4-1BB activation and PD-1 blockade enhances antitumor efficacy in a mouse model of subcutaneous tumor. In: Anticancer Research. 2015 ; Vol. 35, No. 1. pp. 129-136.
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