背景技术免疫抑制被认为是败血症诱导的死亡原因。反编程死亡 - 配体1(PD-L1)治疗在逆转败血症诱导的免疫抑制方面具有很有希望,但没有证据可用于使用市售的抗PD-L1药物进行该指示。进行本发明的临床前研究以研究抗PD-L1纳米体(KN035)在败血症中的治疗效果。材料和方法用流式细胞术确认PD-L1人源化小鼠中PD-L1的表达水平。使用酶联免疫吸附测定检测不同时间点的不同剂量的血浆浓度。将PD-L1人源化小鼠分配为4组:假,盲肠连接和穿刺(CLP),同种型(同种型+ CLP)和PD-L1(KN035 + CLP)。观察到7天的存活率以研究CLP小鼠的结果。通过小鼠肺和肝脏的组织病理学评估评估疾病严重程度。基于细胞凋亡的细胞凋亡评估免疫状态。结果在CLP手术后,外周血淋巴细胞,单核细胞和中性粒细胞显着升高PD-L1水平。 Blood concentrations of KN035 showed that 2.5 mg/kg had potential to be an ideal dosage for KN035 therapy. Survival analysis demonstrated that KN035 was associated with significantly reduced mortality on Day 7 after surgery (P=0.0083). The histopathological tests showed that KN035 alleviated sepsis-induced injury in the lungs and liver. KN035 reduced the number of apoptotic cells in the spleen and almost eliminated bacterial colonies in the peritoneal lavage fluid from the CLP mice. CONCLUSIONS KN035, an anti-PD-L1 antibody, can improve the rate of survival in CLP mice and alleviate sepsis-induced apoptosis in the spleen.
用于最新消息和更新

参考

PubMed.