Trial Watch: Immunostimulatory monoclonal antibodies in cancer therapy

Fernando Aranda, Erika Vacchelli, Alexander Eggermont, Jerome Galon, Wolf Hervé Fridman, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi

Research output: Contribution to journalReview articlepeer-review

103 Citations (Scopus)

Abstract

Immunostimulatory monoclonal antibodies (mAbs) exert antineoplastic effects by eliciting a novel or reinstating a pre-existing antitumor immune response. Most often, immunostimulatory mAbs activate T lymphocytes or natural killer (NK) cells by inhibiting immunosuppressive receptors, such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PDCD1, best known as PD-1), or by engaging co-stimulatory receptors, like CD40, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as OX40) or TNFRSF18 (best known as GITR). The CTLA4-targeting mAb ipilimumab has been approved by the US Food and Drug Administration for use in patients with unresectable or metastatic melanoma in 2011. The therapeutic profile of ipilimumab other CTLA4-blocking mAbs, such as tremelimumab, is currently being assessed in subjects affected by a large panel of solid neoplasms. In the last few years, promising clinical results have also been obtained with nivolumab, a PD-1-targeting mAb formerly known as BMS- 936558. Accordingly, the safety and efficacy of nivolumab and other PD-1-blocking molecules are being actively investigated. Finally, various clinical trials are underway to test the therapeutic potential of OX40- and GITR-activating mAbs. Here, we summarize recent findings on the therapeutic profile of immunostimulatory mAbs and discuss clinical trials that have been launched in the last 14 months to assess the therapeutic profile of these immunotherapeutic agents.

Original languageEnglish
Article numbere27297
JournalOncoImmunology
Volume3
Issue number2
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • CD137
  • Checkpoint blockade
  • Immunogenic chemotherapy
  • Immunosuppression
  • IPH2101
  • Lirilumab
  • PD-L1

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