CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Molecular and immunological determinants of long-term survival in multiple myeloma.
Molecular and immunological determinants of long-term survival in multiple myeloma.
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多发性骨髓瘤(MM)的长期生存(LTS),定义为在接受单一治疗方案后诊断起生存≥10年,由于治疗领域的重大进展,已成为越来越常见的结局。蛋白酶体抑制剂、免疫调节药物、单克隆抗体、自体干细胞移植以及新型免疫疗法的引入,彻底改变了MM的治疗格局。重要的是,仅有一部分患者能够实现长期、持久的疾病控制,这提示骨髓瘤内在机制和免疫介导机制均发挥关键作用。治疗进展,包括CAR-T 细胞疗法和双特异性抗体,主要惠及标危患者。除治疗干预外,LTS似乎还受到免疫骨髓环境(IBME)独特特征的驱动,其中T细胞功能增强、NK 细胞细胞毒性增加以及免疫抑制性髓系细胞群减少共同促进疾病控制。理解LTS MM中的这些免疫适应性变化,为开发下一代治疗策略奠定了基础。未来整合基因组和免疫谱分析以及IBME调控的研究,对于将MM治疗范式从疾病管理转向持续缓解和功能性治愈至关重要。
Long-term survival (LTS) in multiple myeloma (MM), defined as survival of ≥10 years after diagnosis following a single line of therapy, is an increasingly observed outcome due to significant therapeutic advancements. The introduction of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, autologous stem cell transplantation, and novel immunotherapies has transformed MM treatment.
Importantly, only a subset of patients achieves long-term, durable disease control, suggesting that both myeloma-intrinsic and immune-mediated mechanisms play critical roles. Therapeutic advancements, including chimeric antigen receptor T-cell therapy and bispecific antibodies, have primarily benefited standard-risk patients. Beyond therapeutic interventions, LTS appears to be driven by distinct features of the immune bone marrow environment (IBME), in which enhanced T-cell function, increased natural killer cell cytotoxicity, and reduced immunosuppressive myeloid populations contribute to disease control.
Understanding these immune adaptations in LTS MM provides a foundation for developing next-generation treatment strategies. Future research integrating genomic and immune profiling, along with IBME modulation, will be critical in shifting MM treatment paradigms from disease management to sustained remission and functional cures.
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