Mipasetamab

Mipasetamab is an IgG1κ antibody targeting to AXL, a tyrosine kinase receptor and an TAM Receptor. Mipasetamab involves in synthesis of ADCT-601 (Mipasetamab uzoptirine), an AXL-targeted antibody-drug conjugate (ADC). ADCT-601 has anti-tumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> TAM Receptor

AXL[1]

ADCT-601 (0.02-9.29 nM；5 天) 对 AXL 阳性 SN12C 细胞和 AXL 阴性 Karpas-299 细胞显示出细胞毒性[1]。 ADCT-601 (0.83 nM；2-36 小时) 在 SN12C 细胞中时间依赖性地增加 DNA 链间交联水平[1]。 Cell Cytotoxicity Assay[1] Cell Line: AXL-positive SN12C cells: Panc-1, A-172, SK-LU-1, MDA-MB-231, SK-OV-3, NCI-H1299, and SN12C Concentration: Incubation Time: 5 days Result: Showed in vitro cytotoxicity with IC50s of 0.47 nM (Panc-1), 0.59 nM (A-172), 0.02 nM (SK-LU-1), 0.35 nM (MDA-MB-231), 0.11 nM (SK-OV-3), 2.2 nM (NCI-H1299), and 0.83 nM (SN12C), respectively.

ADCT-601 (3 mg/kg、6 mg/kg；静脉注射；单剂量) 在非荷瘤雄性 Sprague-Dawley 大鼠中具有安全性和耐受性[1]。 ADCT-601 (1 mg/kg；静脉注射；每天一次，持续 60 天) 在 MDA-MB-231 TNBC 异种移植模型和 SN12C 肾癌异种移植模型中均对小鼠显示出有效且持续的抗肿瘤活性[1]。 ADCT-601 (0.075、0.15 或 0.3 mg/kg；静脉注射；每天一次，持续 45 天) 在具有异质 AXL 表达的胰腺癌 PDX 模型 (PAXF1657) 中也呈剂量依赖性[1]。 Animal Model: Mouse model with SN12C renal cancer xenograft or MDA-MB-231 TNBC xenograft[1] Dosage: 0.3, 0.6, and 1 mg/kg Administration: Intravenous injection; once daily for 60 days Result: Significantly inhibited the growth of tumor volume in vivo in mouse.

[1]. Zammarchi F, et al. Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody-drug Conjugate Targeting AXL-expressing Cancers. Mol Cancer Ther. 2022 Apr 1;21(4):582-593.