Tebotelimab

Tebotelimab (MGD-013) is a humanized IgG4κ bispecific PD-1/LAG-3 dual-affinity re-targeting (DART) antibody. Tebotelimab binds cell-surface expressed PD-1 and LAG-3 with EC50s of 1.65 nM and 0.41 nM in NS0 cells, respectively. Tebotelimab blocks PD-1/PD-L1, PD-1/PD-L2 and LAG-3/HLA (MHC-II) interactions and PD-1 signaling. Tebotelimab restores exhausted T-cell responses and and enhances antitumour immunity.

MGD013 (0.39, 1.56, 6.25, 25 nM; 48 hours) enhances T-cell antigen receptor-driven Activation in human PBMCs. MGD013 shows enhanced staphylococcal enterotoxin B (SEB; 0.5mg/mL)-induced IFN-γ secretion compared to PD-1 + LAG-3 mAb combination^[1].

References:
[1]. Ross LaMotte-Mohs, et al. Abstract 3217: MGD013, a bispecific PD-1 x LAG-3 Dual-Affinity Re-Targeting (DART®) protein with T-cell immunomodulatory activity for cancer treatment. Cancer Res (2016) 76 (14_Supplement): 3217.
[2]. Daniel Vt Catenacci, et al.MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. Future Oncol. 2021 Apr;17(10):1155-1164.
[3]. Yiming Wei, et al. LAG3-PD-1 Combo Overcome the Disadvantage of Drug Resistance. Front Oncol. 2022 Apr 14;12:831407.