刍议纳米抗体在CAR-T细胞疗法上的应用

Discussion on the Application of Nanoantibodies in CAR-T Cell Therapy

嵌合抗原受体T细胞(CAR-T)是经过基因改造,在其表面表达合成CAR分子的T淋巴细胞。CAR分子赋予T淋巴细胞识别细胞表面靶抗原的能力,并对表达这些抗原的细胞介导特异性细胞毒性。通常,单克隆抗体的单链抗体片段(scFv)被用作CARs的抗原靶向结构域。到目前为止,已有6种CAR-T疗法得到了批准,其中5种CAR-T产品的抗原识别域均基于scFv,只有ciltacabtagene autoleucel使用了单域纳米抗体。然而,单链抗体作为CAR靶向结构域的具有一定的局限性。近年来,研究人员一直在关注其他类型的CAR结构域,包括纳米抗体、肽或配体。其中,纳米抗体作为替代的CAR靶向结构域表现出特别的优势,包括纳米抗体的低免疫原性、稳定性、特异性和高亲和力,以及简单可行的开发过程。许多研究结果证实,在临床前和临床环境中,基于纳米抗体的CAR-Ts可以与基于单链抗体的CAR-Ts发挥同样的功能。

Chimeric antigen receptor T cells(CAR-T)are genetically modified T lymphocytes that express and synthesize CAR molecules on their surface.CAR molecules endow T lymphocytes with the ability to recognize cell surface target antigens and mediate specific cytotoxicity against cells expressing these antigens.Typically,single chain antibody fragments(scFv)of monoclonal antibodies are used as antigen tar⁃geting domains for CARs.So far,6 CAR-T therapies have been approved,of which 5 CAR-T products have antigen recognition domains based on scFv,and only citacaptagen autoleucel uses single domain nanoantibodies.However,single chain antibodies have certain limita⁃tions as CAR targeting domains.In recent years,researchers have been focusing on other types of CAR domains,including nanoantibodies,peptides,or ligands.Among them,nanoantibodies have shown special advantages as alternative CAR targeting domains,including low immunogenicity,stability,specificity,and high affinity of nanoantibodies,as well as a simple and feasible development process.Many research results have confirmed that in preclinical and clinical settings,CAR-Ts based on nanoantibodies can perform the same function as CAR-Ts based on single chain antibodies.