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:CAR-T Cell Therapy in Large B Cell Lymphoma.
大 B 细胞淋巴瘤(LBCL)是最常见的非霍奇金淋巴瘤之一(约占 30%)。
大B细胞淋巴瘤(LBCL)约占非霍奇金淋巴瘤的30%,是最常见的类型之一。尽管这类淋巴瘤具有侵袭性,超过60%的患者可通过一线R-CHOP方案化学免疫治疗治愈。对于难治或复发患者,即使接受二线治疗,结局仍较差。靶向CD19的嵌合抗原受体(CAR)T细胞正成为治疗LBCL的有效二线策略。目前已有3种CD19 CAR-T产品获FDA和EMA批准。CAR-T也已用于高危LBCL一线治疗以及中枢神经系统受累患者的研究。尽管抗CD19 CAR-T改变了复发/难治性LBCL的治疗,但约60%的患者最终仍会进展或复发。因此,确定CAR-T疗效预测标准,并为CAR-T治疗后复发患者开发挽救疗法至关重要。此外,正在开展的临床试验评估同时靶向CD19和CD20或CD19和CD22的双特异性CAR-T,以提高治疗效力并减少难治或复发患者数量。
Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin's lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies. CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. CAR-T cell therapy has also been explored for treating high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement. Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T; therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials evaluate bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and reduce the number of refractory/relapsing patients.
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