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:Sequencing CD19-targeted therapies in patients with relapsed/refractory large B-cell lymphoma: A narrative review.
CD19在早期阶段即表达于B细胞,并在大多数B细胞恶性肿瘤中表达,但在造血干细胞或其他正常组织中不表达,因此使其成为治疗复发或难治性(R/R)大B细胞淋巴瘤患者的一个有吸引力的治疗靶点。
CD19在早期阶段即表达于B细胞,并在大多数B细胞恶性肿瘤中表达,但在造血干细胞或其他正常组织中不表达,因此使其成为治疗复发或难治性(R/R)大B细胞淋巴瘤患者的一个有吸引力的治疗靶点。虽然CD19靶向的CAR-T 细胞疗法、单克隆抗体和抗体-药物偶联物是B细胞淋巴瘤的有效疗法,但R/R环境下的结局可能取决于既往是否接受过针对同一抗原的治疗。关于这些治疗方式序贯应用影响的数据有限。本综述重点介绍近期试验和真实世界数据,这些数据关注CD19靶向药物tafasitamab-lenalidomide和loncastuximab tesirine在R/R B细胞淋巴瘤患者CAR-T治疗前后应用的有效性和安全性,并阐述评估治疗前靶抗原水平以及识别治疗失败的常见分子机制的重要性。此外,本分析讨论了高危疾病患者中未满足的需求以及序贯应用这些治疗策略的挑战,同时提供专家临床实践建议以优化患者结局。
CD19 is expressed on B cells from an early stage and in most B-cell malignancies, but not in hematopoietic stem cells or other normal tissues, thereby making it an attractive therapeutic target for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphomas. While CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapies, monoclonal antibodies, and antibody-drug conjugates are effective therapies for B-cell lymphomas, outcomes in the R/R setting may depend on exposure to prior treatments with the same antigen. There are limited data on the impact of sequencing these treatment modalities. This review highlights recent trial and real-world data focusing on the efficacy and safety of the CD19-targeted agents tafasitamab-lenalidomide and loncastuximab tesirine before and after CAR-T therapy in patients with R/R B-cell lymphoma and addresses the importance of assessing pretreatment target antigen levels as well as identifying common molecular mechanisms of treatment failure. Additionally, this analysis discusses the unmet needs in patients with high-risk disease and the challenges of sequencing these therapeutic strategies, while providing expert clinical practice recommendations to optimize patient outcomes.
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