Our B7-H6/CD3 T-cell engager is currently undergoing clinical investigation in Phase I studies as a monotherapy and in combination with ezabenlimab (BI 754091)*, a programmed cell death protein-1 (PD-1) inhibitor, in patients with advanced solid tumors that express B7-H6.^2–4

B7-H6/CD3 T-cell engager clinical trials

B7-H6/CD3 T-cell engager mechanism of action

The pharmacologic effect of the B7-H6/CD3 T-cell engager depends on its simultaneous binding to both the CD3 subunit of the T-cell receptor complex as well as to B7-H6 on tumor cells targeted for elimination. This results in lysis of B7-H6–positive target cells, activation and proliferation of T cells, and secretion of cytokines. The B7-H6/CD3 T-cell engager does not block interaction of B7-H6 with its natural ligand Nkp30, allowing B7-H6–dependent NK-cell activation and cytotoxicity.⁵
 

B7-H6/CD3 T-cell engager mechanism of action^5,6

Combination therapy

In humanized CRC mouse models, monotherapy with our B7-H6/CD3 T-cell engager resulted in dose-dependent antitumor activity, infiltration of T-cells, and upregulation of the PD-(L)1 pathway in the tumor tissue; therefore, combination with anti-PD-1 agents (such as ezabenlimab) may further enhance the efficacy of the B7-H6/CD3 T-cell engager.^5,6

B7-H6 is a member of the B7 family of immune receptors and is expressed in several solid tumors and cancers including CRC, gastric cancer, and pancreatic cancer. No to very little B7-H6 expression can be detected in normal tissues. This suggests B7-H6 may be an ideal target for a tumor-selective approach.^1,7

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
CD3, cluster of differentiation 3; CRC, colorectal cancer; NK, natural killer; PD-1, programmed cell death protein-1;  PD-L1; programmed death ligand-1; PDAC, pancreatic ductal adenocarcinoma.