{"title":"[CAR T 细胞疗法治疗髓系恶性肿瘤的现状与前景]。","authors":"Shoji Saito","doi":"10.11406/rinketsu.65.634","DOIUrl":null,"url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy is among the most promising immunotherapies for hematological malignancies and can be used to treat myeloid malignancies in practice. However, developing CAR-T therapies for such diseases is particularly challenging due to the heterogeneity of target antigen expression across leukemic cells and patients, the difficulty in excluding on-target/off-target tumor effects, and the immunosuppressive tumor microenvironment. To date, various targets, including CD33, NKG2D, CD123, CLL-1, and CD7, have been actively studied for CAR-T cells, especially for acute myeloid leukemia (AML). Although no CAR-T cell products have been approved, several clinical trials have shown promising results, particularly for those targeting CLL-1 and CD123. Furthermore, new ideal targets and use of allogeneic or off-the-shelf CAR-T cell products are under investigation. Meanwhile, it remains unknown whether CAR-T therapy would be effective for other myeloid malignancies, including myelodysplastic syndromes and myeloproliferative diseases. This review discusses challenges in the development of CAR-T therapy for myeloid malignancies, especially for AML, from the perspectives of target antigen characteristics and disease-specific on-target/off-tumor toxicity. Moreover, it discusses the clinical development and prospects of CAR-T cells for these diseases.</p>","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Current state and future prospects of CAR T-cell therapy for myeloid malignancies].\",\"authors\":\"Shoji Saito\",\"doi\":\"10.11406/rinketsu.65.634\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Chimeric antigen receptor (CAR)-T cell therapy is among the most promising immunotherapies for hematological malignancies and can be used to treat myeloid malignancies in practice. However, developing CAR-T therapies for such diseases is particularly challenging due to the heterogeneity of target antigen expression across leukemic cells and patients, the difficulty in excluding on-target/off-target tumor effects, and the immunosuppressive tumor microenvironment. To date, various targets, including CD33, NKG2D, CD123, CLL-1, and CD7, have been actively studied for CAR-T cells, especially for acute myeloid leukemia (AML). Although no CAR-T cell products have been approved, several clinical trials have shown promising results, particularly for those targeting CLL-1 and CD123. Furthermore, new ideal targets and use of allogeneic or off-the-shelf CAR-T cell products are under investigation. Meanwhile, it remains unknown whether CAR-T therapy would be effective for other myeloid malignancies, including myelodysplastic syndromes and myeloproliferative diseases. This review discusses challenges in the development of CAR-T therapy for myeloid malignancies, especially for AML, from the perspectives of target antigen characteristics and disease-specific on-target/off-tumor toxicity. Moreover, it discusses the clinical development and prospects of CAR-T cells for these diseases.</p>\",\"PeriodicalId\":93844,\"journal\":{\"name\":\"[Rinsho ketsueki] The Japanese journal of clinical hematology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"[Rinsho ketsueki] The Japanese journal of clinical hematology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.11406/rinketsu.65.634\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"[Rinsho ketsueki] The Japanese journal of clinical hematology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.11406/rinketsu.65.634","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
[Current state and future prospects of CAR T-cell therapy for myeloid malignancies].
Chimeric antigen receptor (CAR)-T cell therapy is among the most promising immunotherapies for hematological malignancies and can be used to treat myeloid malignancies in practice. However, developing CAR-T therapies for such diseases is particularly challenging due to the heterogeneity of target antigen expression across leukemic cells and patients, the difficulty in excluding on-target/off-target tumor effects, and the immunosuppressive tumor microenvironment. To date, various targets, including CD33, NKG2D, CD123, CLL-1, and CD7, have been actively studied for CAR-T cells, especially for acute myeloid leukemia (AML). Although no CAR-T cell products have been approved, several clinical trials have shown promising results, particularly for those targeting CLL-1 and CD123. Furthermore, new ideal targets and use of allogeneic or off-the-shelf CAR-T cell products are under investigation. Meanwhile, it remains unknown whether CAR-T therapy would be effective for other myeloid malignancies, including myelodysplastic syndromes and myeloproliferative diseases. This review discusses challenges in the development of CAR-T therapy for myeloid malignancies, especially for AML, from the perspectives of target antigen characteristics and disease-specific on-target/off-tumor toxicity. Moreover, it discusses the clinical development and prospects of CAR-T cells for these diseases.