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双特异性抗体与 CAR-T 疗法在多发性骨髓瘤中的现状

英文原题:Current status of bispecific antibodies and CAR-T therapies in multiple myeloma.

查看英文原题

Current status of bispecific antibodies and CAR-T therapies in multiple myeloma.

PubMed 2024/05/10(内容时间) Int Immunopharmacol Q1 · IF 5.6(JCR 2025)

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中文摘要

多发性骨髓瘤(MM)是一种浆细胞恶性肿瘤,无法治愈,其特征为浆细胞肿瘤性增殖并造成广泛骨骼破坏,包括溶骨性病变、骨量减少和病理性骨折。临床表现包括骨痛、肾功能不全、高钙血症、贫血和反复感染。MM 患病率及对有效治疗的需求凸显了相关研究的重要性。近期 MM 治疗取得重大进展,尤其是 daratumumab 纳入一线治疗。将 daratumumab 用于 DRD(daratumumab、Revlimid、dexamethasone)和 D-RVd(daratumumab、lenalidomide、bortezomib、dexamethasone)等方案,代表治疗格局的转变。GRIFFIN 和 CASSIOPEIA 试验显示这些方案有效,特别是在延长无进展生存期和加深患者应答方面。治疗策略已从 MPV(melphalan、prednisone、Velcade)等旧方案转向 DRD 和 RVD 等更有效方案。本综述还关注CAR-T 细胞疗法和双特异性抗体治疗 MM 的潜力。CAR-T 已成功用于其他血液系统恶性肿瘤,目前正探索其特异性靶向 MM 细胞的能力。文章分析最新临床试验和研究结果,以评估 CAR-T 治疗 MM 的疗效与挑战,并探讨可同时结合癌细胞和 T 细胞、可能补充 CAR-T 效果的双特异性抗体。

展开英文摘要原文

Multiple myeloma (MM), a malignancy of plasma cells, is an incurable disease that is characterized by the neoplastic proliferation of plasma cells leading to extensive skeletal destruction. This includes osteolytic lesions, osteopenia, and pathologic fractures. MM is clinically manifested through bone pain, renal insufficiency, hypercalcemia, anemia, and recurrent infections. Its prevalence and the need for effective treatment underscore the importance of this research. Recent advancements in MM therapy have been significant, particularly with the integration of daratumumab into first-line treatments. The use of daratumumab in regimens such as DRD (Daratumumab, Revlimid, Dexamethasone) and D-RVd (Daratumumab, Lenalidomide, Bortezomib, Dexamethasone) represents a paradigm shift in the treatment landscape.

GRIFFIN and CASSIOPEIA trials have highlighted the efficacy of these regimens, particularly in prolonging progression-free survival and deepening patient responses. The shift from older regimens like MPV (Melphalan, Prednisone, Velcade) to more effective ones like DRD and RVD has been pivotal in treatment strategies.

This review also focuses on the potential of Chimeric Antigen Receptor T-cell therapy and bispecific antibodies in MM. CAR-T therapy, which has shown success in other hematological malignancies, is being explored for its ability to specifically target MM cells. The latest clinical trials and research findings are analyzed to evaluate the efficacy and challenges of CAR-T therapy in MM.

Additionally, the role of bispecific antibodies, which are designed to bind both cancer cells and T cells, is explored. These antibodies offer a unique mechanism that could complement the effects of CAR-T therapy.

论文信息

作者
Szlasa W、Dybko J
第一作者单位
Lower Silesia Centre for Oncology, Pulmonology and Hematology in Wrocław, 53-439 Wroclaw, Poland; Medical University Hospital, Borowska 213, 50-556, Wrocław, Poland; Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland.Poland
通讯作者单位
Lower Silesia Centre for Oncology, Pulmonology and Hematology in Wrocław, 53-439 Wroclaw, Poland; Department of Oncology and Hematology, Wroclaw University of Science and Technology, 50-370 Wrocław, Poland. Electronic address: jaroslaw.dybko@dcopih.pl.Poland
文献类型
综述
期刊
International immunopharmacology2024 Jun 15
原文标识
PubMed 38733817 · DOI 10.1016/j.intimp.2024.112043