案例信息

标题：CD3双特异性抗体药物的研究与评价

【专业学位类别】公共卫生

【专业领域/方向】生物化学与分子生物学

【作者】

【单位】厦门大学公共卫生学院

【关键词】肿瘤免疫疗法；CD3双特异性抗体；T细胞活化

【适用课程】

【版权说明】真实性案例，仅用于教学目的

【案例摘要】恶性肿瘤是当前严重威胁人类健康的重大公共卫生问题之一。免疫疗法是一种新兴的肿瘤治疗策略，其中CD3双特异性抗体被认为是最有希望的治疗策略之一。本项目设计了一种囊泡化T细胞衔接器，将针对T细胞CD3分子及肝癌细胞特异性膜抗原GPC3的双特异性抗体定向展示在细胞膜囊泡上，并在囊泡内部负载由氢氧化铝佐剂吸附IL-2所形成的纳米颗粒，成功制备了AI@VITE复合囊泡。结果显示AI@VITE能够特异性的引导T细胞到肝癌细胞周围，诱发T细胞活化和增殖并诱导极强的免疫反应。AI@VITE在免疫缺陷鼠移植异种癌细胞的小鼠模型和在免疫健全的人源CD3转基因小鼠模型中展现了显著的抑瘤效果。相关研究为抗体药物研究及肿瘤免疫治疗带来新的突破。

Title: 

Professional Degree Category: Master of Public Health

Specialized fields: 

Authors: 

Affiliation: School of Public Health, Xiamen University

Key words: Cancer immunotherapy; CD3 bispecific antibody；T cell activation

Abstract

Cancer is one of the major public health problems that seriously threaten human health. Immunotherapy is an emerging strategy for cancer treatment, among which CD3 bispecific antibodies are considered one of the most promising therapeutic strategies. This project has designed a vesicle-based T cell engager that directionally presents a bispecific antibody targeting T cell CD3 molecules and the liver cancer cell-specific membrane antigen GPC3 on the surface of cell membrane vesicles. Additionally, it loads nanoparticles formed by the adsorption of IL-2 on aluminum hydroxide adjuvant within the vesicle, successfully creating the AI@VITE composite vesicles. The results show that AI@VITE can specifically guide T cells to the vicinity of liver cancer cells, induce T cell activation and proliferation, and trigger a robust immune response. AI@VITE has demonstrated significant tumor suppression effects in an immunodeficient mouse xenograft model and an immunocompetent human CD3 transgenic mouse model. This research brings breakthroughs to the development of antibody drug and cancer immunotherapy.

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