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:Emerging treatment strategies for newly diagnosed diffuse large B-cell lymphoma.
尽管近期在改善患者生存方面取得进展,但约 40% 的弥漫大 B 细胞淋巴瘤(DLBCL)患者结局仍然不佳。
尽管近年来患者生存有所改善,仍约有40%的弥漫性大B细胞淋巴瘤(DLBCL)患者结局较差。多年来,R-CHOP(利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松)一直是DLBCL一线标准治疗;近期,pola-R-CHP(泊洛妥珠单抗维多汀、利妥昔单抗、环磷酰胺、多柔比星和泼尼松)成为新的治疗选择。与此同时,针对高危DLBCL相关信号通路、细胞抗原及表观遗传调控因子的新型分子靶向疗法正在开发。研究者还在探索依据细胞起源或特定分子亚型定制治疗,采用亚型特异性靶向药物。此外,已在复发或难治性DLBCL中显示疗效的药物——如抗CD19抗体他法西他单抗及免疫调节药物golcadomide——目前也在新诊断患者中研究。包括抗CD19CAR-T 细胞疗法和CD20×CD3双特异性抗体(BsAb)在内的免疫疗法,显著改善了复发或难治患者的结局,目前正在评估作为早期治疗的效果。BsAb可支持更灵活的治疗策略,包括与细胞毒性治疗或无化疗方案联合。本综述总结了新诊断DLBCL新型治疗策略的近期进展及在研试验,这些疗法可能很快纳入临床实践。
Despite recent progress in improving patient survival, the outcomes in approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) remain poor. For many years, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard first-line treatment for DLBCL; however, pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) has recently emerged as a new treatment option. In parallel, novel molecularly targeted therapies that target signaling pathways, cellular antigens, and epigenetic regulators associated with high-risk DLBCL are in development. Treatment strategies tailored to the cell of origin or to specific molecular subtypes are also being explored using subtype-specific targeted agents. In addition, agents that have demonstrated efficacy in patients with relapsed or refractory DLBCL-such as the anti-CD19 antibody tafasitamab and immunomodulatory drugs such as golcadomide-are currently under investigation for use in newly diagnosed patients. Immunotherapies, including anti-CD19-chimeric antigen receptor-T therapy and CD20 CD3 bispecific antibodies (BsAbs), have significantly improved outcomes in patients with relapsed or refractory disease and are now under evaluation as early-line therapies. BsAbs can enable more flexible treatment strategies, including combination regimens with cytotoxic or chemotherapy-free approaches. This review summarizes recent advances and ongoing trials that are investigating novel therapeutic strategies for newly diagnosed DLBCL that may soon be incorporated into clinical practice.
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