肿瘤细胞治疗研究
英文原题:Development of BCMA-Targeted Bispecific Natural Killer Cell Engagers for Multiple Myeloma Treatment.
Development of BCMA-Targeted Bispecific Natural Killer Cell Engagers for Multiple Myeloma Treatment.
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靶向B细胞成熟抗原(BCMA)的T细胞重定向免疫疗法,包括嵌合抗原受体(CAR)T细胞疗法和T细胞衔接器,在治疗浆细胞恶性肿瘤复发/难治性(RR)多发性骨髓瘤(MM)方面已取得显著成功。然而,这些疗法可能导致T细胞过度活化,并引发细胞因子释放综合征和神经毒性,这是MM患者面临的重要挑战。双特异性NK细胞衔接器(NKCE)或可作为有前景的替代方案,通过将NK细胞的细胞毒活性重定向至肿瘤细胞,而不触发细胞因子释放综合征。
本研究设计了一系列BCMA/CD16 NKCE,分别同时结合MM细胞上的BCMA和NK细胞上的CD16,并根据分子结构在体外评估其功能。
结果表明,NKCE的结构形式会影响其功能,凸显了选择合适分子形式对于优化MM的NKCE治疗至关重要。本研究为开发下一代NKCE以及推进MM和其他潜在恶性肿瘤的治疗策略提供了重要见解。
B-cell maturation antigen (BCMA)-targeted T cell-redirecting immunotherapies, including Chimeric Antigen Receptor (CAR) T-cell therapy and T-cell engagers have demonstrated remarkable success in treating relapsed/refractory (RR) multiple myeloma (MM), a malignancy of plasma cells. However, a significant challenge is the severe side effects associated with T-cell overactivation, leading to cytokine release syndrome and neurotoxicity in MM patients undergoing such therapies. Bispecific NK cell engagers (NKCEs) may offer a promising alternative by redirecting NK cell cytotoxic activity towards tumor cells without triggering cytokine release syndrome.
In this study, we designed a series of BCMA CD16 NKCEs that simultaneously engage BCMA and CD16 on MM and NK cells, respectively. We evaluated the functionality of these NKCEs in vitro with respect to their molecular design.
Our results indicate that the format design of NKCEs influences their functionalities, underscoring the importance of format selection in optimizing NKCE-based therapies for MM. This study provides valuable insights for developing next-generation NKCEs and advancing therapeutic strategies for MM and potentially other malignancies.
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