人源化CD73抗体筛选及活性研究
Screening and Activity Study of Humanized CD73 Antibody
赵丽丽 1孙士民 1朱中松 1张贵民 2刘忠2
作者信息
- 1. 鲁南新时代生物技术有限公司,山东临沂 273400;哺乳动物细胞高效表达国家工程实验室,山东临沂 273400
- 2. 鲁南制药集团股份有限公司,山东临沂 276000
- 折叠
摘要
CD73抗体可以遏制肿瘤发展和转移,但其靶点和疗效研究较少,且目前没有上市的抗体药物.该研究通过对鼠源CD73抗体进行人源化改造,并进一步通过小鼠实体瘤模型研究其药效.结果显示,人源化的CD73抗体20huM51有较高的亲和力和中和活性.该抗体能逆转AMP介导的抑制CD4+T/CD8+T释放IFN-γ的作用,从而促进IFN-γ的分泌.在20 mg/kg的给药剂量下,该抗体在小鼠体内具有显著的抗肿瘤作用,肿瘤体积抑制率和肿瘤质量抑制率分别为26.3％和21.6％.本研究为CD73抗体药物的临床前研发提供了数据支持.
Abstract
Anti-CD73 antibody can inhibit tumor development and metastasis,but there are few studies on its targets and efficacy,and there is no antibody drug on the market at present.In this study,a murine CD73 antibody was humanized,and its efficacy in a mouse solid tumor model was further studied.The results showed that the humanized anti-CD73 20huM51 antibody had a high affinity and neutralizing activity.The anti-CD73 antibody reversed the AMP-mediated inhibition on the release of IFN-y by CD4+T/CD8+T cells and promoted the secretion of IFN-y.At a dose of 20 mg/kg,the antibody had a significant antitumor activity in mice.The tumor volume and weight inhibition rates were 26.3％and 21.6％,respectively.This study provided data support for the preclinical development of anti-CD73 drugs.
关键词
CD73单克隆抗体/抗肿瘤活性/杂交瘤/人源化抗体/药效Key words
CD73 monoclonal antibody/antitumor activity/hybridoma/humanized antibody/pharmacodynamics引用本文复制引用
基金项目
山东省重点研发计划(泰山产业领军人才工程)(tscy20200329)
山东省重点研发计划(泰山产业领军人才工程)(tscx202306088)
出版年
2024
NETL
NSTL
万方数据