CAJ | 학술논문

目的应用3种不同的细胞毒素与CD103单克隆抗体(M290)制备抗体-药物偶联物(ADCs),从中筛选出高效低毒、体内能杀伤CD103表达细胞的ADCs,用来阻断CD103/E-钙黏蛋白(E-cadherin)信号途径.方法选取MC-MMAF、SMCC-DM1、MC-vc-PAB-MMAE与M290制备出3种不同毒素的ADCs.3种ADCs分别以2、2、6 mg/kg的剂量经腹腔注入C57BL/6小鼠体内,用流式细胞术筛选能够杀伤CD103表达细胞的ADCs,通过动态监测小鼠体质量和临床症状评价药物毒性.对照组注射磷酸盐缓冲液(PBS)、M290、M290-SAP.结果 3种ADCs均具有高效低毒的体内杀伤CD103表达细胞的能力,ADCs给药组小鼠小肠上皮内淋巴细胞绝对数与注射PBS组比较显著减少(P＜0.01).结论 3种ADCs均能有效阻断CDl03/E-cadherin信号途径.
목적 응용3충불동적세포독소여CD103단극륭항체(M290)제비항체-약물우련물(ADCs),종중사선출고효저독、체내능살상CD103표체세포적ADCs,용래조단CD103/E-개점단백(E-cadherin)신호도경.방법 선취MC-MMAF、SMCC-DM1、MC-vc-PAB-MMAE여M290제비출3충불동독소적ADCs.3충ADCs분별이2、2、6 mg/kg적제량경복강주입C57BL/6소서체내,용류식세포술사선능구살상CD103표체세포적ADCs,통과동태감측소서체질량화림상증상평개약물독성.대조조주사린산염완충액(PBS)、M290、M290-SAP.결과 3충ADCs균구유고효저독적체내살상CD103표체세포적능력,ADCs급약조소서소장상피내림파세포절대수여주사PBS조비교현저감소(P＜0.01).결론 3충ADCs균능유효조단CDl03/E-cadherin신호도경.
Objective To generate optional antibody-drug conjugates (ADCs) using three different cytotoxic agents and monoclonal antibody (M290) which can efficiently deplete CD103 + cells in vivo with reduced off-target toxicity.The ADCs will be utilized to block the CD103 pathway to determine therapeutic potential in islet allograft rejection.Methods The CD103 monoclonal antibody (M290) was conjugated with MMAF,MMAE or DMI to generate M290-MC-MMAF,M290-vc-PAB-MMAE or M290-MCC-DM1.ADCs were injected intraperitoneally respectively by dose of 2,2,6 mg/kg into C56BL/6 mice,then the depletion efficacy in vivo was evaluated by flow cytometry.The toxicity of ADCs was tested in wild mice by weight monitoring and symptoms.The mice were divided into PBS,M290,M290-SAP and ADCs groups.Results All ADCs resulted in potently depletion of CD103 + cells in vivo with high specificity and less toxicity.The number of intraepithelial lymphocytes of ADCs groups was significantly less than that in PBS group (P ＜0.01).Conclusion The three ADCs were potencial drugs that block CD103/E-cadherin pathway.