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Talacotuzumab (JNJ 56022473) is an IgG1 fully humanized CD123 neutralizing monoclonal antibody containing a modified Fc structure. Talacotuzumab has a high affinity for CD123, CD32b/c, CD16-158F and CD16-158V, with KD of 0.43 nM, 188 nM, 46 nM and 16.8 nM, respectively. Talacotuzumab inhibits IL-3 signaling in target cells by inhibiting IL-3 binding to CD123. Talacotuzumab induces mutations in the Fc region to increase affinity for CD16 (FCγriiia), thereby enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Talacotuzumab inhibits leukemia cell growth in xenografted mouse models of acute myeloid leukemia (AML).
説明 | Talacotuzumab (JNJ 56022473) is an IgG1 fully humanized CD123 neutralizing monoclonal antibody containing a modified Fc structure. Talacotuzumab has a high affinity for CD123, CD32b/c, CD16-158F and CD16-158V, with KD of 0.43 nM, 188 nM, 46 nM and 16.8 nM, respectively. Talacotuzumab inhibits IL-3 signaling in target cells by inhibiting IL-3 binding to CD123. Talacotuzumab induces mutations in the Fc region to increase affinity for CD16 (FCγriiia), thereby enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Talacotuzumab inhibits leukemia cell growth in xenografted mouse models of acute myeloid leukemia (AML). |
ターゲット&IC50 | TF-1 cells:33 pM |
In vitro |
With an IC50 of 5 ng/ml (33 pM), Talacotuzumab (JNJ 56022473; CSL 362) potently mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in TF-1 cells [1]. Following a 24-hour pretreatment at 1 μg/ml,Talacotuzumab inhibits the production of IFN-α in plasmacytoid dendritic cells and eosinophils in SLE (systemic lupus erythematosus) donor and healthy donor plasma-like dendritic cells. This inhibition occurs when these cells are stimulated with TLR7 (imiquimod; 0.5 μM; 6 days) and TLR9 (CpG C; 0.5 μM; 6 days). However, Talacotuzumab does not significantly reduce IFN-α production induced by TLR4 stimulation (LPS; 10 μg/ml). The inhibitory effect of Talacotuzumab on plasmacytoid dendritic cell (pDC) proliferation and expansion induced by TLR7 and TLR9 is achieved through the depletion of pDC [2]. |
In vivo |
In mice with xenografts of acute myeloid leukemia,Talacotuzumab (JNJ 56022473; CSL 362; 300 μg; intraperitoneal injection; three times per week for 5 weeks) significantly delays tumor growth compared to the isotype control [1]. Talacotuzumab (1, 10, 30 mg/kg; subcutaneous injection; single dose) in juvenile cynomolgus monkeys reaches maximum serum concentrations of 12, 190, and 380 μg/ml at doses of 1, 10, and 30 mg/kg, respectively, within 48 hours [2]. |
別名 | CSL 362, JNJ 56022473 |
分子量 | N/A |
CAS No. | 1826831-79-1 |
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Talacotuzumab 1826831-79-1 Immunology/Inflammation Immunology/Inflammation related Interleukin CSL362 CSL-362 JNJ-56022473 JNJ56022473 CSL 362 JNJ 56022473 Inhibitor inhibitor inhibit