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Review
. 2019 Jun 12;4(Suppl 3):e000510.
doi: 10.1136/esmoopen-2019-000510. eCollection 2019.

New emerging targets in cancer immunotherapy: the role of Cluster of Differentiation 40 (CD40/TNFR5)

Manuel Piechutta  1 , Anna Sophie Berghoff  2
Affiliations
Review

New emerging targets in cancer immunotherapy: the role of Cluster of Differentiation 40 (CD40/TNFR5)

Manuel Piechutta et al. ESMO Open. .

Abstract

Cluster of differentiation 40 (CD40) is a member of the tumour necrosis factor family and a new immune-modulating target in cancer treatment. B cells, myeloid cells and dendritic cells can express CD40 and mediate via the ligand cluster of differentiation 40 ligand (CD40L) cytotoxic T cell priming under physiological conditions. Therapeutically, recombinant CD40L molecules, intratumour application of adenoviral vectors leading to CD40L expression and agonistic monoclonal CD40 antibodies are currently tested in various cancer entities for their immune-modulating potential. Early clinical trials suggest safety for agonistic CD40 antibodies with encouraging antitumour effects. Adverse events encompass cytokine release storm, hepatoxicity, thromboembolic events and were so far reported to be clinically manageable and transient. Ongoing studies investigate CD40 activation in combination with chemotherapy, radiation, targeted therapies and immunomodulatory agents. Further studies are awaited to specifically identify patients with the greatest clinical benefit based on predictive biomarkers.

Keywords: APX005M; CD40; CP-870,893; TNFR5; cluster of differentiation 40; immune checkpoint inhibitor; immune modulating cancer therapy; selicrelumab.

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Conflict of interest statement

Competing interests: ASB has research support from Daiichi Sankyo, Hoffmann La-Roche and honoraria for lectures, consultation or advisory board participation from Roche, Bristol-Meyers Squibb, Merck, Daiichi Sankyo as well as travel support from Roche, Amgen and AbbVie.

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