Therapeutics: Delta-like 1 (DLL1); immunoglobulin G (IgG)

Studies in mice suggest complexes of DLL1, biotinylated anti-IgG antibodies and the biotin-binding protein avidin could help treat lung cancer. In mouse xenograft models of lung cancer, multiple complexes consisting of DLL1-Fc fusion proteins bound to biotinylated anti-IgG antibodies and avidin in multivalent clusters increased T cell infiltration of tumors and decreased tumor vascularization and growth compared with anti-IgG antibody/avidin complexes lacking the DLL1-Fc fusion proteins. In a transgenic mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer, the DLL1 complexes plus Tarceva erlotinib decreased tumor size and increased progression-free survival compared with control complexes plus Tarceva. Next steps include PK/PD and toxicology studies...