Liu Peipei, Gu Chunyin, Cao Xiaodan, Zhang Huawei, Wang Zongda, Yang Yukun, OuYang KeDong, Zhen Yingying, Jia Fangfang, He Xianqing, Yu Haixiang, Deng Sujun
Biologics Innovation Institute, Shanghai Jemincare Pharmaceutical Co., Ltd., Lane 535, Huanqiao Road, Pudong New Area, Shanghai 201315, China.
Antib Ther. 2024 Oct 10;8(1):1-12. doi: 10.1093/abt/tbae027. eCollection 2025 Jan.
Therapeutic antibody drugs targeting the PD-1 pathway are generally characterized by relatively low response rates and susceptibility to drug resistance during clinical application. Therefore, there is an urgent need for alternative therapeutic strategies to increase the immune response rate. Bispecific antibodies co-targeting PD-1 and PD-L1 may have greater potential to improve the efficacy of the immune checkpoint pathway.
In this study, we developed a potent humanized common light chain (CLC) IgG shape bispecific antibody (bsAb), named JMB2005, based on Hybridoma-to-Phage-to-Yeast platform. The platform allowed us to discover CLC bsAb from traditional mice for any pair of given targets.
JMB2005 exhibited favorable developability, good manufacturing property, and satisfactory efficacy, which could be given via subcutaneous injection at the concentration of 120 mg/mL. Mechanistically, JMB2005 could bridge tumor cells and T cells with both Fab arms and promote T-cells to function as direct tumor cell killers. It could also promote T cell activation by blocking the binding of PD-L1 to CD80. Furthermore, JMB2005 has exhibited a favorable half-life and has demonstrated promising anti-tumor therapeutic efficacy .
Consequently, the present study showed that the novel humanized CLC bsAb JMB2005 may represent a novel therapeutic agent of great clinical potential.
靶向PD-1通路的治疗性抗体药物在临床应用中通常具有相对较低的反应率和耐药性。因此，迫切需要替代治疗策略来提高免疫反应率。同时靶向PD-1和PD-L1的双特异性抗体可能具有更大的潜力来提高免疫检查点通路的疗效。
在本研究中，我们基于杂交瘤-噬菌体-酵母平台开发了一种高效的人源化共轻链（CLC）IgG型双特异性抗体（bsAb），命名为JMB2005。该平台使我们能够从传统小鼠中发现针对任何一对给定靶点的CLC bsAb。
JMB2005具有良好的可开发性、良好的生产特性和令人满意的疗效，可通过皮下注射给予，浓度为120mg/mL。从机制上讲，JMB2005可以通过两个Fab臂连接肿瘤细胞和T细胞，并促进T细胞作为直接的肿瘤细胞杀手发挥作用。它还可以通过阻断PD-L1与CD80的结合来促进T细胞活化。此外，JMB2005具有良好的半衰期，并已显示出有前景的抗肿瘤治疗效果。
因此，本研究表明新型人源化CLC bsAb JMB2005可能是一种具有巨大临床潜力的新型治疗药物。
