{"title":"CAR T 细胞治疗 T 细胞急性淋巴细胞白血病","authors":"Marie Emilie Dourthe , André Baruchel","doi":"10.1016/j.ejcped.2024.100150","DOIUrl":null,"url":null,"abstract":"<div><p>T-cell acute lymphoblastic leukemia (T-ALL) has a dismal prognosis in case of relapsed or refractory disease. Contrary to B-ALL, few immunotherapies are available for T-ALL. Use of autologous CAR T-cells is challenging due to shared antigen between leukemic and normal T-cells responsible for fratricide and T-cell aplasia in case of persistence of CAR T-cells. Moreover, risk of contamination of the apheresis product by lymphoblasts remains an issue. To counteract these challenges several methods are used to edit T-cell such as protein expression blocker, CRISPR/Cas9 and base-editing. Other possibility is to use autologous T-cells naturally selected <em>in vitro</em> or donor-derived T-cells allowing gene edition and reduction of the risk of graft vs host disease. Encouraging results are obtained in preclinical and clinical studies for early response rate but several questions remain. Is the persistence of these cells requiring for maintaining the remission? Is it feasible to recover a target-negative T-cell population without risk of profound immunosuppression? Has an allogeneic stem cell transplantation to be planned for patients after CAR T-cells infusion? What about the risk of engineered T-cells in the long term?</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"3 ","pages":"Article 100150"},"PeriodicalIF":0.0000,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000096/pdfft?md5=43b91a189526444cfcf248b29b55d17c&pid=1-s2.0-S2772610X24000096-main.pdf","citationCount":"0","resultStr":"{\"title\":\"CAR T-cells for T-cell acute lymphoblastic leukemia\",\"authors\":\"Marie Emilie Dourthe , André Baruchel\",\"doi\":\"10.1016/j.ejcped.2024.100150\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>T-cell acute lymphoblastic leukemia (T-ALL) has a dismal prognosis in case of relapsed or refractory disease. Contrary to B-ALL, few immunotherapies are available for T-ALL. Use of autologous CAR T-cells is challenging due to shared antigen between leukemic and normal T-cells responsible for fratricide and T-cell aplasia in case of persistence of CAR T-cells. Moreover, risk of contamination of the apheresis product by lymphoblasts remains an issue. To counteract these challenges several methods are used to edit T-cell such as protein expression blocker, CRISPR/Cas9 and base-editing. Other possibility is to use autologous T-cells naturally selected <em>in vitro</em> or donor-derived T-cells allowing gene edition and reduction of the risk of graft vs host disease. Encouraging results are obtained in preclinical and clinical studies for early response rate but several questions remain. Is the persistence of these cells requiring for maintaining the remission? Is it feasible to recover a target-negative T-cell population without risk of profound immunosuppression? Has an allogeneic stem cell transplantation to be planned for patients after CAR T-cells infusion? What about the risk of engineered T-cells in the long term?</p></div>\",\"PeriodicalId\":94314,\"journal\":{\"name\":\"EJC paediatric oncology\",\"volume\":\"3 \",\"pages\":\"Article 100150\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-02-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2772610X24000096/pdfft?md5=43b91a189526444cfcf248b29b55d17c&pid=1-s2.0-S2772610X24000096-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJC paediatric oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2772610X24000096\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJC paediatric oncology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772610X24000096","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
T细胞急性淋巴细胞白血病(T-ALL)复发或难治的预后很差。与 B-ALL 相反,T-ALL 可用的免疫疗法很少。使用自体 CAR T 细胞具有挑战性,因为白血病 T 细胞和正常 T 细胞之间存在共享抗原,在 CAR T 细胞持续存在的情况下会导致自相残杀和 T 细胞增生。此外,淋巴母细胞污染血液净化产品的风险仍然是一个问题。为了应对这些挑战,有几种方法可用于编辑 T 细胞,如蛋白表达阻断剂、CRISPR/Cas9 和碱基编辑。另一种方法是使用体外自然选择的自体 T 细胞或供体来源的 T 细胞,这样可以进行基因编辑,降低移植物与宿主疾病的风险。临床前和临床研究在早期反应率方面取得了令人鼓舞的结果,但仍存在几个问题。维持缓解是否需要这些细胞的持续存在?恢复靶阴性T细胞群而不造成严重免疫抑制的风险是否可行?是否计划为输注 CAR T 细胞后的患者进行异体干细胞移植?工程T细胞的长期风险如何?
CAR T-cells for T-cell acute lymphoblastic leukemia
T-cell acute lymphoblastic leukemia (T-ALL) has a dismal prognosis in case of relapsed or refractory disease. Contrary to B-ALL, few immunotherapies are available for T-ALL. Use of autologous CAR T-cells is challenging due to shared antigen between leukemic and normal T-cells responsible for fratricide and T-cell aplasia in case of persistence of CAR T-cells. Moreover, risk of contamination of the apheresis product by lymphoblasts remains an issue. To counteract these challenges several methods are used to edit T-cell such as protein expression blocker, CRISPR/Cas9 and base-editing. Other possibility is to use autologous T-cells naturally selected in vitro or donor-derived T-cells allowing gene edition and reduction of the risk of graft vs host disease. Encouraging results are obtained in preclinical and clinical studies for early response rate but several questions remain. Is the persistence of these cells requiring for maintaining the remission? Is it feasible to recover a target-negative T-cell population without risk of profound immunosuppression? Has an allogeneic stem cell transplantation to be planned for patients after CAR T-cells infusion? What about the risk of engineered T-cells in the long term?