MK-5890 had monotherapy efficacy in these models and enhanced efficacy of PD-1 blockade. Functional Fc-receptor interaction was required to activate CD8+ T cells in an ex vivo tumor explant system and to induce antitumor efficacy in syngeneic murine subcutaneous tumor models. MK-5890 activated CD27 expressed on 293T NF-κB luciferase reporter cells and, conditional on CD3 stimulation, in purified CD8+ T cells without the requirement of crosslinking.

Crystallization studies revealed that MK-5890 binds to a unique epitope in the cysteine-rich domain 1 (CRD1).

Results Humanized anti-CD27 antibody MK-5890 (hIgG1) was shown to bind human CD27 on the cell surface with sub-nanomolar potency and to partially block binding to its ligand, CD70.

7 Process Research and Development, Merck & Co Inc, Kenilworth, New Jersey, USA.

6 Discovery, Preclinical and Translational Medicine, Merck & Co Inc, West Point, Pennsylvania, USA.

5 Clinical Development, Merck & Co Inc, Rahway, New Jersey, USA.

4 Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

3 Discovery, Preclinical and Translational Medicine, Merck & Co Inc, South San Francisco, California, USA.

2 Discovery, Preclinical and Translational Medicine, Merck & Co Inc, Kenilworth, New Jersey, USA.

1 BioNovion/Aduro Biotech Europe, Oss, The Netherlands.

Graphpad prism trial activate registry