双特异性抗体免疫疗法在胶质母细胞瘤治疗中的研究进展

Research advances in bispecific antibody immunotherapy in treatment of glioblastoma

摘要:

胶质母细胞瘤（GBM）的治疗因免疫抑制微环境、血脑屏障（BBB）阻隔及高度异质性而面临严峻挑战，对免疫检查点抑制剂（ICIs）等传统疗法反应不佳。双特异性抗体（BsAb）通过同时桥接T细胞与肿瘤抗原（如EGFRvⅢ、HER2、B7-H3等），在临床前研究中展现出克服GBM治疗困境的潜力。该综述系统分析了BsAb（包括双特异性T细胞衔接器BiTE）在GBM治疗中的研究进展与作用机制。如靶向上述抗原的BsAb能有效激活T细胞、促进其肿瘤浸润并特异性杀伤GBM细胞，提高多种临床前模型（如原位异种移植模型、人源化模型）的生存率；以及BiTE疗法在诱导持久抗肿瘤效应方面亦显示出前景。

Abstract:

There are still significant challenges in the treatment of glioblastoma （GBM） due to the immunosuppressive microenvironment， the blood-brain barrier （BBB）， and high heterogeneity， and there is a poor responses to conventional therapies such as immune checkpoint inhibitors （ICIs）. Bispecific antibody （BsAb）， which can simultaneously bridge T cells and tumor antigens （such as EGFRvⅢ， HER2， and B7-H3）， have shown certain potential in overcoming the therapeutic challenges of GBM in preclinical studies. This article systematically reviews the research advances and mechanisms of action of BsAb， including bispecific T-cell engager （BiTE）， in the treatment of GBM. Studies have shown that BsAb targeting the aforementioned antigens can effectively activate T cells， promote their tumor infiltration， and specifically kill GBM cells， thereby significantly improving survival rates in various preclinical models （such as orthotopic xenograft models and humanized models）， and BiTE therapy has also shown promise in inducing durable antitumor effects.