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:Beyond BCMA: newer immune targets in myeloma.
Beyond BCMA: newer immune targets in myeloma.
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通过抗体-药物偶联物、CAR-T 细胞和T细胞衔接器等免疫治疗策略对B细胞成熟抗原(BCMA)的识别和靶向,已经彻底改变了多发性骨髓瘤(MM)患者的治疗。与既往 established 策略相比,这些治疗方式改善了复发和/或难治性MM患者的生存结局,并正在向更早的治疗线次推进。尽管这些疗法有效,大多数患者最终仍会复发,因此需要额外的治疗靶点用于挽救治疗。G蛋白偶联受体C类5组成员D、Fc受体同源物5和SLAMF7是正在开发中的一些新靶点示例。这一不断扩展的免疫治疗药物库将对于解决BCMA靶向治疗后复发这一未满足需求至关重要,尤其是抗原阴性复发。使用序贯性T细胞重定向疗法,包括靶向不同肿瘤相关抗原的药物和联合疗法,似乎是可行的,为有效的无化疗方案铺平了道路。审慎考虑治疗时机、保护T细胞健康、克服抗原丢失以及对复杂肿瘤微环境的理解,将是最大化治疗获益和最小化不良反应的关键。本综述总结了骨髓瘤中BCMA之外正在开发的新靶点,在可获得时呈现来自临床试验的关键安全性和有效性数据,以及在这一不断扩展的免疫治疗选择领域中导航所必需的重要考虑因素。
The identification and targeting of B-cell maturation antigen (BCMA) through immunotherapeutic strategies such as antibody-drug conjugates, chimeric antigen receptor T cells, and T-cell engagers have revolutionized the care of patients with multiple myeloma (MM). These treatment modalities have improved the survival outcomes of patients with relapsed and/or refractory MM compared with previously established strategies and are moving into earlier lines of therapy. Despite their efficacy, the majority of patients eventually relapse, necessitating additional therapeutic targets for salvage. G-protein-coupled receptor class 5 member D, Fc receptor-homolog 5, and SLAMF7 are some examples of novel targets in development.
This expanding armamentarium of immunotherapeutic agents will be crucial to address the unmet need for relapses after BCMA-targeting therapies, particularly antigen-negative relapses. The utilization of sequential T-cell redirective therapies including agents targeting different tumor-associated antigens and combination therapies appears feasible, paving the way for effective chemotherapy-free regimes.
Deliberate consideration of treatment timing, preserving T-cell health, overcoming antigenic loss, and comprehension of the complex tumor microenvironment would be key to maximizing therapeutic benefits and minimizing adverse effects. This review summarizes novel targets in development for myeloma beyond BCMA, presenting pivotal safety and efficacy data derived from clinical trials when available and the considerations vital for navigating this expanding landscape of immunotherapeutic options.
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