Citatuzumab bogatox

Citatuzumab bogatox (VB6-845) is recombinant immunotoxin that composed of Fab fragment of humanized antibody targeting EpCAM and a modified cytotoxin bouganin. Citatuzumab bogatox binds to and selectively induces Apoptosis in EpCAM-positive cell lines and shows good activity in EpCAM-positive human tumour xenograft models[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Citatuzumab bogatox (0-100 nM; 5 days) 抑制 NIH:OVCAR-3 和 CAL-27 细胞的生长，IC50 值均为 3 nM[1]。 Citatuzumab bogatox内化到 EpCAM 表达细胞的细胞质中，然后释放的 Bouganin 通过核糖体失活抑制蛋白质合成，导致癌细胞凋亡[2]。 Cell Viability Assay[1] Cell Line: NIH:OVCAR-3 and CAL-27 cells Concentration: 0-100 nM Incubation Time: 5 days Result: Exhibited an IC50 of 3 nM to against the EpCAM-positive cell lines.

Citatuzumab bogatox (10, 20 mg/kg; i.v./i.p.) 抑制小鼠体内肿瘤生长[1]。 Citatuzumab bogatox (10, 20 mg/kg) 在小鼠体内显示很好的耐受性，并无任何明显的体重下降[1]。 Animal Model: Female CB.17 SCID mice (~20 g; OVCAR-3 Xenograft model)[1]. Dosage: 10, 20 mg/kg Administration: Tail vein (until day 26 when due to tail swelling, route of administration was changed to intraperitoneal for the remaining 7 doses); single daily for 5 consecutive days for 3 weeks and then received maintenance dosing on Monday and Friday for 4 weeks. Result: Showed an average of 40 mm3 (control group was 750 mm3) on day 75, and with 3/15 mice being tumor free, when at 10 mg/kg. Almost completely inhibited tumour growth when at 20 mg/kg.

[1]. Cizeau J, et al. Engineering and biological characterization of VB6-845, an anti-EpCAM immunotoxin containing a T-cell epitope-depleted variant of the plant toxin bouganin. J Immunother. 2009 Jul-Aug;32(6):574-84.  

[2]. Eyvazi S, et al. Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update. Curr Cancer Drug Targets. 2018;18(9):857-868.  

[3]. Bruce VJ, et al. Minimalist Antibodies and Mimetics: An Update and Recent Applications. Chembiochem. 2016 Oct 17;17(20):1892-1899.