Pacanalotamab (AMG 420; BI-836909) is a bispecific T-cell engager (BiTE) targeting to BCMA and CD3E. BCMA refers to B cell maturation antigen, as Pacanalotamab redirecting T cells to BCMA expressing cells on the cell surface. Pacanalotamab conducts T-cell redirected lysis of human multiple myeloma (MM) cell lines.
Pacanalotamab (1 pg/mL-100 ng/mL; 24 h) induces BCMA-dependent tumor cell lysis via T cells activation. And Pacanalotamab induces dose-dependent redirected lysis of human multiple myeloma cell lines with EC90 values ranging from 16-810 pg/mL[1]. Pacanalotamab (100 ng/mL; 24 h) induces translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane, leading to apoptosis in MM.1R cells[1].
Pacanalotamab (50 μg/kg/day; i.v. or s.c.; for 18 days) exhibits anti-tumor activity in mouse NCI-H929 xenograft model[1]. Pacanalotamab (5 μg/kg/day; i.v. or s.c.) significant prolongs survival of mouse in mouse orthotopic L-363 xenograft model[1]. Pacanalotamab (135 μg/kg/day for i.v. or 405 μg/kg/day for s.c.; up to 28 days) is well tolerated, and it decreases plasma cells in the bone marrow in macaque in toxicity studies[1].
References:
[1]. Hipp S, et al. A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia. 2017 Aug;31(8):1743-1751.