About our DLL3/CD3 T-cell engager
Mechanism of action
Our compound acts as a T-cell engager with an extended half-life.1 The DLL3/CD3 T-cell engager directs the activity of cytolytic T cells selectively to DLL3-expressing tumors.1-3
The pharmacological effect of the DLL3/CD3 T-cell engager depends on its ability to bind simultaneously to CD3 on T-cells and to DLL3 expressed on tumor cells, resulting in the formation of a cytolytic synapse.1,2
Preclinical studies have demonstrated the antitumor activity of DLL3/CD3 T-cell engager in a range of DLL3-positive tumor models.2,3 In preclinical studies, DLL3/CD3 monotherapy potently inhibited tumor growth in DLL3-positive SCLC xenograft models in a dose-dependent and time-dependent manner. It also modulated the inflammatory environment in the tumor tissue by redirecting CD4-positive and CD8-positive T-cell cytotoxicity toward DLL3-postitive SCLC cells, without affecting DLL3-negative target cells.2
T-cell engager mechanism of action1,3
Watch the T-cell engager mechanism of action animation
Combination therapy
The binding of the DLL3/CD3 T-cell engager to CD3 may lead to programmed cell death protein 1 (PD-1) upregulation in activated T cells and programmed death-ligand 1 upregulation on malignant cells.2 Preclinical evidence supports the combination of the DLL3/CD3 T-cell engager with PD-1 inhibitors (such as ezabenlimab) in order to revert this upregulation.1,2
Boehringer Ingelheim. Data on file.
Hipp S, et al. Clin Cancer Res. 2020;26:5258–5268.
Wermke M, et al. ASCO 2021. Poster TPS8588.