title: Rationale for anti-OX40 cancer immunotherapy.
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.
authors.affiliation: 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.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Aspeslagh
authors.affiliation: DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France; University Paris Sud XI, Kremlin Bicêtre, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.affiliation: INSERM U1015, Gustave Roussy Cancer Institute, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France; University Paris Sud XI, Kremlin Bicêtre, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: 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.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: DITEP, Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France; INSERM U1015, Gustave Roussy Cancer Institute, Villejuif, France. Electronic address: aurelien.marabelle@gustaveroussy.fr.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D053262:Receptors, OX40 / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D000911:Antibodies, Monoclonal; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human
keywords: CD134; Cancer; Immune checkpoint; Immunotherapy; OX40