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Lipei Wang^1,2, Mingqian Zhou^1,3, Xiangyu Kong^1,3

¹Division of Immunotherapy, The Hiram C. Polk, Jr. MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.

International journal of molecular sciences

|September 9, 2023

概括

针对信号传感器和转录3激活剂 (STAT3) 采用新型结合剂有效降低了B细胞淋巴瘤的生长. 这种STAT3siRNA合体通过抑制瘤进展在体外和体内表现出治疗淋巴瘤的前景.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

信号传感器和转录3激活器 (STAT3) 的构成性激活与瘤发生有关,特别是在淋巴瘤中.
STAT3在调节多种瘤过程中发挥着至关重要的作用,使其成为B细胞恶性瘤的潜在治疗标.

研究的目的:

开发和评估一种新型的结合物,用于针对性地将STAT3小干扰RNA (siRNA) 传递给B细胞淋巴瘤.
评估STAT3siRNA结合体在抑制淋巴瘤细胞增殖和瘤生长中的疗效,在体外和体内.

主要方法:

构建一种抗CD19-SMCC-原胺 (CSP) -STAT3siRNA结合体,用于有针对性的输送.
在体外评估对B细胞和淋巴瘤细胞系的结合结合特异性 (A20,SU-DHL-2,OCI-Ly3).
在接受治疗的淋巴瘤细胞中评估STAT3表达,细胞增殖,S相分数和细胞亡.
使用A20移植性淋巴瘤模型进行体内研究,以评估瘤生长抑制和分子标记物 (Ki-67,p-STAT3,STAT3,IL-6).

主要成果:

在实验室中,CSP-STAT3 siRNA合体表现出与正常B细胞和A20淋巴瘤细胞的特定结合.
结合剂的治疗显著降低了STAT3表达,减少了淋巴瘤细胞增殖,降低了S相分数,并增加了亡.
在体内,结合剂在A20淋巴瘤模型中显著抑制瘤生长和体重,降低了Ki-67,p-STAT3,STAT3和IL-6的水平.

结论:

通过使用CSP结合物将STAT3siRNA向B细胞淋巴瘤的向输送有效地降低了STAT3活性.
这种方法在体外和体内显著抑制了淋巴瘤的进展,证明了治疗潜力.
开发的STAT3siRNA结合体代表了治疗B细胞淋巴瘤的有希望的策略.

关键词:

B 细胞 B 细胞 B 细胞在SMCC中,SMCC是SMCC.在STAT3中,我们可以使用STAT3.结合式的结合式的淋巴瘤淋巴瘤是什么 siRNA 是一个RNA.

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