Tang Tiffany C Y, Xu Ning, Nordon Robert, Haber Michelle, Micklethwaite Kenneth, Dolnikov Alla
Graduate School of Biomedical Engineering, Faculty of Engineering, UNSW Sydney, Sydney, NSW, Australia.
Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, Sydney, NSW, Australia.
Biomark Res. 2022 Apr 1;10(1):14. doi: 10.1186/s40364-022-00359-3.
Adoptive cell therapy using patient-derived chimeric receptor antigen (CAR) T cells redirected against tumor cells has shown remarkable success in treating hematologic cancers. However, wider accessibility of cellular therapies for all patients is needed. Manufacture of patient-derived CAR T cells is limited by prolonged lymphopenia in heavily pre-treated patients and risk of contamination with tumor cells when isolating T cells from patient blood rich in malignant blasts. Donor T cells provide a good source of immune cells for adoptive immunotherapy and can be used to generate universal off-the-shelf CAR T cells that are readily available for administration into patients as required. Genome editing tools such as TALENs and CRISPR-Cas9 and non-gene editing methods such as short hairpin RNA and blockade of protein expression are currently used to enhance CAR T cell safety and efficacy by abrogating non-specific toxicity in the form of graft versus host disease (GVHD) and preventing CAR T cell rejection by the host.
采用针对肿瘤细胞重定向的患者来源嵌合受体抗原（CAR）T细胞进行的过继性细胞治疗在治疗血液系统癌症方面已取得显著成功。然而，需要让所有患者更广泛地获得细胞疗法。患者来源的CAR T细胞的制造受到严重预处理患者长期淋巴细胞减少的限制，以及从富含恶性母细胞的患者血液中分离T细胞时肿瘤细胞污染的风险。供体T细胞为过继性免疫治疗提供了良好的免疫细胞来源，可用于生成通用的现货型CAR T细胞，这些细胞可根据需要随时用于给患者给药。目前，诸如转录激活样效应因子核酸酶（TALENs）和CRISPR-Cas9等基因组编辑工具以及诸如短发夹RNA和蛋白质表达阻断等非基因编辑方法，被用于通过消除移植物抗宿主病（GVHD）形式的非特异性毒性以及防止宿主对CAR T细胞的排斥反应，来提高CAR T细胞的安全性和疗效。
