Rationale for anti-OX40 cancer immunotherapy

Sandrine Aspeslagh, Sophie Postel-Vinay, Sylvie Rusakiewicz, Jean-Charles Soria, Laurence Zitvogel, Aurélien Marabelle

Research output: Contribution to journalScientific review

195 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)50-66
Number of pages17
JournalEuropean Journal of Cancer
Volume52
DOIs
Publication statusPublished - Jan 2016

Bibliographical note

Copyright © 2015 Elsevier Ltd. All rights reserved.

Keywords

  • Animals
  • Antibodies, Monoclonal/adverse effects
  • Humans
  • Immunotherapy/adverse effects
  • Neoplasms/drug therapy
  • Receptors, OX40/antagonists & inhibitors
  • Signal Transduction/drug effects
  • Treatment Outcome
  • Tumor Microenvironment

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