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Rationale for anti-OX40 cancer immunotherapy

  • Sandrine Aspeslagh
    Affiliations
    DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France

    Ghent University Hospital, Department of Oncology, De Pintelaan 185, 9000 Ghent, Belgium
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  • Sophie Postel-Vinay
    Affiliations
    DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France

    University Paris Sud XI, Kremlin Bicêtre, France
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  • Sylvie Rusakiewicz
    Affiliations
    INSERM U1015, Gustave Roussy Cancer Institute, Villejuif, France
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  • Jean-Charles Soria
    Affiliations
    DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France

    University Paris Sud XI, Kremlin Bicêtre, France
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  • Laurence Zitvogel
    Affiliations
    DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France

    INSERM U1015, Gustave Roussy Cancer Institute, Villejuif, France

    University Paris Sud XI, Kremlin Bicêtre, France

    CIC Biothérapie IGR Curie CIC1428, Gustave Roussy Cancer Institute, Villejuif, France
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  • Aurélien Marabelle
    Correspondence
    Corresponding author: DITEP and UMR1015, Gustave Roussy Cancer Centre, 114 rue Edouard Vaillant, 94805 Villejuif cedex, France.
    Affiliations
    DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France

    INSERM U1015, Gustave Roussy Cancer Institute, Villejuif, France
    Search for articles by this author
Published:November 29, 2015DOI:https://doi.org/10.1016/j.ejca.2015.08.021

      Highlights

      • Combination of anti-OX40 therapy with different anti-cancer agents is very promising.
      • Anti-OX40 therapy does target intratumoural regulatory T-cells.
      • Anti-OX40 should be seen as a novel adjuvant.

      Abstract

      Immune checkpoint blockade with antagonistic monoclonal antibodies (mAbs) targeting B7 immunoglobulin superfamily molecules (CTLA-4, PD-1, and PD-L1) generate long lasting anti-tumour immune responses translating into clinical benefit across many cancer types. However, many patients are primarily resistant to immune checkpoint blockade –based monotherapy and many others will eventually relapse. Therefore, new immunostimulatory targets are needed to overcome primary and secondary resistance to immunotherapy. Besides the B7 co-inhibitory receptors, the tumour necrosis factor receptor superfamily contains many other immune checkpoints, which could become the next generation immunomodulators. Among them stands OX40 (CD134), a co-stimulatory molecule that can be expressed by activated immune cells. Several anti-OX40 agonistic monoclonal antibodies are currently tested in early phase cancer clinical trials. Accumulating preclinical evidence supports their clinical development. However, conflicting results and controversies between in vitro and in vivo data point to the need for comprehensive ancillary studies to be performed in upcoming clinical trials to better understand the mechanism of action of anti-OX40 mAbs-based therapy.

      Keywords

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