癌症研究
免疫原性
免疫检查点
免疫疗法
封锁
单克隆抗体
医学
抗体
PD-L1
联合疗法
免疫系统
抗原
T细胞
癌症免疫疗法
免疫学
药理学
受体
内科学
作者
Rui Zhang,Zhiyan Zhu,Hongying Lv,Futian Li,Shuangqing Sun,Juan Li,Chun‐Sing Lee
出处
期刊:Small
[Wiley]
日期:2019-11-08
卷期号:15 (49)
被引量:128
标识
DOI:10.1002/smll.201903881
摘要
Abstract Targeting programmed cell death protein 1 (PD‐1)/programmed death ligand 1 (PD‐L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However, therapeutic antibodies exhibit several issues such as limited tumor penetration, immunogenicity, and costly production. Here, Bristol‐Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS‐202 is a small‐molecule inhibitor of the PD‐1/PD‐L1 interaction that is developed by BMS. Transfer of BMS‐202 NPs to 4T1 tumor‐bearing mice results in markedly slower tumor growth to the same degree as treatment with anti‐PD‐L1 monoclonal antibody (α‐PD‐L1). Consistently, the combination of Ce6 NPs with BMS‐202 NPs or α‐PD‐L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen‐specific T cells into the tumors. Thus, inhibition rates of primary and distant tumors reach >90%. In addition, BMS‐202 NPs are able to attack spreading metastatic lung tumors and offer immune‐memory protection to prevent tumor relapse. These results indicate that BMS‐202 NPs possess effects similar to α‐PD‐L1 in the therapies of 4T1 tumors. Therefore, this work reveals the possibility of replacing the antibody used in immunotherapy for tumors with BMS‐202 NPs.
科研通智能强力驱动
Strongly Powered by AbleSci AI