PO.PR02.01 · 预防研究
具有肿瘤细胞毒性的全人源抗PD-L1抗体:在SmocMab小鼠中的筛选
Fully human anti-PD-L1 antibodies with tumor cytotoxicity: Screening in SmocMab mice
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
PD-L1在广泛的肿瘤细胞谱中高表达,并负向调节T细胞的肿瘤细胞毒性。在此,我们利用对免疫球蛋白重链和轻链可变区人源化的SmocMab小鼠,通过单B细胞筛选生成了多种具有高结合亲和力的全人源抗PD-L1抗体。这些抗体在体外有效阻断了PD-1/PD-L1相互作用,并表现出强大的内吞活性。在体内研究中,抗PD-L1抗体单药治疗在hPD1 C57BL/6小鼠中显示出显著的肿瘤抑制效果。此外,基于这些抗PD-L1抗体构建的PD-L1抗体药物偶联物(ADC)大幅增强了肿瘤杀伤效力。总之,这些发现验证了SmocMab小鼠可作为筛选具有良好治疗潜力的全人源抗体的稳健平台。
查看英文原文 English abstract
PD-L1 is highly expressed across a broad spectrum of tumor cells and negatively regulates the tumor cytotoxicity of T cells. Herein, we generated multiple fully human anti-PD-L1 antibodies with high binding affinity through single B cell screening, utilizing SmocMab mice humanized for the variable regions of immunoglobulin heavy and light chains. These antibodies effectively blocked the PD-1/PD-L1 interaction in vitro and exhibited potent endocytic activity. In in vivo studies, monotherapy with the anti-PD-L1 antibodies demonstrated significant tumor-suppressive effects in hPD1 C57BL/6 mice. Furthermore, PD-L1 antibody-drug conjugates (ADCs) constructed based on these anti-PD-L1 antibodies substantially enhanced tumor-killing efficacy. Collectively, these findings validate that SmocMab mice serve as a robust platform for the screening of fully human antibodies with promising therapeutic potential.
利益披露 Disclosure
N. Ge,
Shanghai Model Organisms Center, Inc. Other, Parent Company.
H. He,
Shanghai Model Organisms Center, Inc. Other, Parent Company.
L. Ci,
Shanghai Model Organisms Center, Inc. Other, Parent Company.
R. Sun,
Shanghai Model Organisms Center, Inc. Other, Parent Company.
D. Feng,
Shanghai Model Organisms Center, Inc. Other, Parent Company.