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多发性骨髓瘤中的双特异性抗体靶点与疗法

英文原题:Bispecific antibody targets and therapies in multiple myeloma.

查看英文原题

Bispecific antibody targets and therapies in multiple myeloma.

PubMed 2024/10/10(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

近期,多种双特异性抗体(BsAb)在早期临床试验中显示出高缓解率和令人瞩目的单药无进展生存期,因此已获批用于复发性多发性骨髓瘤(MM)。这些 BsAb 为复发患者提供重要治疗选择,也给临床医生带来了复杂决策。关于此类疗法的最佳患者群体、治疗顺序和疗程,目前证据尚不明确,正在积极研究中。BsAb 的细胞因子释放综合征和神经毒性发生率似乎低于 CAR-T 细胞,但感染导致的患病负担较高,且长期 BsAb 治疗的选择压力会产生新的治疗耐药途径。此外,目前正在积极研究大量具有独特抗体结构和抗原靶点的新型 T 细胞衔接器,早期结局数据令人鼓舞。本综述考察 BsAb 治疗 MM 的作用机制、治疗靶点、联合治疗策略、序贯治疗及疾病复发机制。

展开英文摘要原文

Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation.

While rates of cytokine release syndrome and neurotoxicity appear to be lower with BsAbs than with CAR T-cells, morbidity from infection is high and novel pathways of treatment resistance arise from the longitudinal selection pressure of chronic BsAb therapy.

Lastly, a wealth of novel T-cell engagers with unique antibody-structures and antigenic targets are under active investigation with promising early outcome data. In this review, we examine the mechanism of action, therapeutic targets, combinational approaches, sequencing and mechanisms of disease relapse for BsAbs in MM.

论文信息

作者
Rees M、Abdallah N、Yohannan B、Gonsalves WI
单位
Division of Hematology, Mayo Clinic, Rochester, MN, United States.United States
文献类型
综述
期刊
Frontiers in immunology2024
原文标识
PubMed 39450163 · DOI 10.3389/fimmu.2024.1424925