摘要
嵌合抗原受体T (chimeric antigen receptor T,CAR-T)细胞疗法在血液系统肿瘤的治疗中取得了显著成就。然而,由于CAR-T细胞的体外制备过程复杂且成本高昂,加之在实体肿瘤治疗中面临靶向浸润困难、免疫抑制环境以及潜在的毒性副作用等科学问题,其治疗效果并不尽如人意。幸运的是,纳米技术的进步为这一领域带来了新的希望。特别是纳米药物递送系统,已成为抗肿瘤药物研发中一个极为活跃的研究方向。本文聚焦于CAR-T疗法与实体肿瘤治疗的相关背景,系统地综述了近年来纳米技术在体外与体内CAR-T细胞制备和实体瘤治疗中的应用,并对未来的发展方向进行了前瞻性的展望。
Chimeric antigen receptor T(CAR-T)cell therapy is an innovative and cutting-edge treatment in the field of adoptive cell therapy.It represents an important milestone in personalized and precision medicine.T cell immunotherapy has gone through more than 30 years of development,making CAR-T cell therapy increasingly mature.Currently,CAR-T cell therapy has achieved significant success in the treatment of hematological system tumors,and the FDA has approved 6 CAR-T cell therapies for the treatment of hematopoietic cancers.However,on one hand,the preparation of CAR-T cells is a highly technical process involving multiple steps,each requiring precise operation and strict condition control to ensure the quality and activity of the cells.The high-quality materials,specialized equipment,and highly specialized personnel required in the production process have led to very high preparation costs for CAR-T cell therapy.The high cost has led to increased treatment fees,which may limit the popularization and accessibility of CAR-T therapy.On the other hand,CAR-T cell therapy faces a series of difficulties and challenges in the treatment of solid tumors.The first is the insufficient targeting and infiltration ability of CAR-T cells to tumors.The tumor microenvironment(TME)of solid tumors is usually composed of dense extracellular matrix,forming a physical barrier that severely limits the targeting and penetration ability of CAR-T cells to tumors.The second is the immunosuppressive factors in the TME.In the TME,there are a large number of immunosuppressive factors,such as interleukin-10,transforming growth factor-β,and suppressive cells including regulatory T cells,tumor-associated macrophages,and myeloid-derived suppressor cells.These factors not only weaken the persistence of CAR-T cells but also severely hinder their effective anti-tumor effect.Finally,CAR-T cell therapy can cause serious cytotoxicity.The activation of CAR-T cells may cause cytokine release syndrome and attack normal cells expressing the CAR-T target antigen,
作者
徐霖
胡泊
郑露露
蒋邵平
阮少波
黄渊余
XU Lin;HU Bo;ZHENG Lu-Lu;JIANG Shao-Ping;RUAN Shao-Bo;HUANG Yuan-Yu(School of Life Science,Advanced Research Institute of Multidisciplinary Science,Beijing Institute of Technology,Beijing 100081,China)
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2024年第12期3103-3122,共20页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金(32171394,82302387)资助项目。
