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Oncoimmunology. 2014 Jan 1;3(1):e27297. Epub 2014 Feb 1.

Trial Watch: Immunostimulatory monoclonal antibodies in cancer therapy.

Author information

1
Gustave Roussy; Villejuif, France ; INSERM, U848; Villejuif, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France.
2
Gustave Roussy; Villejuif, France ; INSERM, U848; Villejuif, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France ; Université Paris-Sud/Paris XI; Paris, France.
3
Gustave Roussy; Villejuif, France.
4
Université Paris Descartes/Paris V ; Sorbonne Paris Cité; Paris, France ; Université Pierre et Marie Curie/Paris VI; Paris, France ; INSERM, U872; Paris, France ; Equipe 15, Centre de Recherche des Cordeliers; Paris, France.
5
Université Pierre et Marie Curie/Paris VI; Paris, France ; INSERM, U872; Paris, France ; Equipe 13, Centre de Recherche des Cordeliers; Paris, France.
6
Gustave Roussy; Villejuif, France ; INSERM, U1015; CICBT507; Villejuif, France.
7
Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP; Paris, France ; Metabolomics and Cell Biology Platforms; Gustave Roussy; Villejuif, France ; INSERM, U848; Villejuif, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France ; Université Paris Descartes/Paris V ; Sorbonne Paris Cité; Paris, France.
8
Gustave Roussy; Villejuif, France ; Université Paris Descartes/Paris V ; Sorbonne Paris Cité; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France.

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.

KEYWORDS:

CD137; IPH2101; PD-L1; checkpoint blockade; immunogenic chemotherapy; immunosuppression; lirilumab

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