决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Recent advances in cell therapy for AML/MDS.
细胞免疫治疗已经极大地改变了B细胞白血病、淋巴瘤和多发性骨髓瘤的治疗。
细胞免疫治疗已显著改变了B细胞白血病、淋巴瘤和多发性骨髓瘤的治疗。嵌合抗原受体(CAR)-T细胞治疗在这些疾病中的成功得益于合适的靶抗原,包括B细胞恶性肿瘤中的CD19和多发性骨髓瘤中的B细胞成熟抗原。相比之下,急性髓系白血病(AML)和骨髓增生异常综合征(MDS)尚未取得类似的进展,部分原因在于尚未找到一种理想靶点,其对正常细胞的靶向效应在临床上可控。尽管如此,找到合适的靶点仍有望推动CAR-T细胞治疗在髓系恶性肿瘤中取得重大治疗进展。为了进一步挖掘细胞免疫治疗在AML/MDS中的潜力,可能需要采取多方面的策略。在开发CAR-T细胞的同时,CAR-NK细胞、T细胞受体工程化T细胞、NK细胞及其他先天免疫方法也在积极探索之中,而异基因造血干细胞移植仍是AML/MDS一种成熟的细胞免疫治疗形式。这些方法可以并行发展,并在适当情况下与分子靶向治疗及其他药物治疗相整合。本期Progress in Hematology综述了这些新兴方向及其拓展AML/MDS细胞治疗的潜力。
Cellular immunotherapy has substantially changed the treatment of B-cell leukemias, lymphomas, and multiple myeloma. The success of chimeric antigen receptor (CAR)-T cell therapy in these diseases has been supported by suitable target antigens, including CD19 in B-cell malignancies and B-cell maturation antigen in multiple myeloma. In contrast, comparable progress has not yet been achieved in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), in part because an optimal target with clinically manageable on-target effects on normal cells has not been identified. Nevertheless, identification of an appropriate target could enable major therapeutic advances with CAR-T cell therapy in myeloid malignancies. To further harness the potential of cellular immunotherapy in AML/MDS, a multifaceted approach may be required. In parallel with CAR-T cell development, CAR-NK cells, T-cell receptor-engineered T cells, NK cells and other innate immune approaches are actively explored, while allogeneic hematopoietic stem cell transplantation remains an established form of cellular immunotherapy for AML/MDS. These approaches may be developed in parallel and, where appropriate, integrated with molecularly targeted and other pharmacologic therapies. This issue of Progress in Hematology reviews these emerging directions and their potential to expand cellular therapy for AML/MDS.
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