Clin Cancer Res: New hope for dual-specific DLL3 targeted T-cell binding agent AMG 757, small cell lung cancer?

Small cell lung cancer (SCLC) is an invasive neuroendocrine tumor with high recurrence rate, limited treatment options and poor prognosis.
δ-like liges 3 (DLL3) are selectively expressed in small cell lung cancer and rarely in normal tissues.
AMG757 is a two-specific T-cell binding molecule that targets the half-life extension of DLL3.
study was designed to assess the anti-tumor activity of AMG 757.
the activity of AMG 757 in SCLC cell line, in-place, and patient-sourced Xeno-transplant (PDX) mouse SCLC models.
the changes in tumor volume in mice after AMG 757 was given, the pharmacological changes in tumor-immersed T-cells (TIL), and the spatial relationship between the emergence of TIL and tumor histology.
to assess tolerance in non-human primates (NHPs).
AMG 757 activates T cells and promotes the production of leukocyte mesogen AMG 757 with strong specific killer effects on SCLC cell strains, even for SCLC cells with very low DLL3 expression ( sl;1000/cells).
AMG 757 can effectively systematically aggregate injected human T cells, induce their resuming, and redirect T cells to dissolved tumor cells, thus promoting the SCLC mouse PDX model and established in-place models of primary pulmonary SCLC and metastasis liver lesions to show significant tumor subsidion and complete remission.
AMG 757 inhibits tumor growth and promotes receding in the NHP model, even at the maximum test dose (4.5 mg/kg/week), the AMG 757 performs well and no adverse reactions associated with AMG 757 are found.
AMG 757 has an extended half-life in the NHP model, the finding suggests that the drug may be applied intermittently.
, in preclinical studies, the AMG 757 demonstrated convincing safety and effectiveity, making it a potential potential choice for clinically targeted SCLCs expressed in DL3.