In Vitro: Talacotuzumab (JNJ 56022473; CSL 362) strongly mediates ADCC of TF-1 cells with an ic50 of 5 ng/ml (33 pM). Talacotuzumab (1 μg/ml; pretreatment for 24 hours) inhibits TLR7-stimulated (Imiquimod; HY-B0180; 0.5 μM; for 6 days) and TLR9-stimulated (CpG C; 0.5 μM; for 6 days) IFN-α production in both SLE donors and healthy donors plasmacytoid dendritic cells (pDCs) and basophils, whereas TLR4-stimulated (LPS; HY-D1056; 10 μg/ml) production is not significantly reduced. Talacotuzumab inhibits TLR7- and TLR9-induced plasmablast expansion and proliferation by depletion of plasmacytoid dendritic cells (pDCs).
In Vivo: Talacotuzumab (JNJ 56022473; CSL 362; 300 μg; ip; thrice weekly for 5 weeks) results in a significant delay in tumor growth compared with an isotype control in acute myeloid leukaemia mice xenografts. Talacotuzumab (1, 10, 30 mg/kg; s.c.; single injection) has maximal serum concentrations at 48 hours of ~12, 190, and 380 μg/ml at doses of 1, 10, and 30 mg/kg in naive cynomolgus monkeys, respectively.