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改善了膀癌抗瘤疗效与重组BCG,释放一个STING激动剂的激动剂

Peter K Um¹, Monali Praharaj^1,2, Kara A Lombardo³

¹Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, USA.

bioRxiv : the preprint server for biology

|January 3, 2024

概括

一种新型的复合巴氏卡尔梅特-盖林 (BCG) 疗法,BCG-disA-OE,通过释放一种STING激动剂,对膀癌 (BC) 显示出增强的抗瘤疗效. 这种修改后的BCG在临床前模型中也显示出更好的安全性.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
微生物学微生物学

背景情况:

静脉 Calmette-Guérin (BCG) 是一种主要治疗非肌肉侵入性膀癌 (BC) 的方法.
需要新的治疗策略来提高BCG在膀癌管理中的有效性和安全性.

研究的目的:

为了评估复合BCG菌株BCG-disA-OE的抗瘤疗效和安全性,该菌株被改造以释放STING激动剂c-di-AMP.
在膀癌模型中研究BCG-disA-OE增强治疗效果的潜在机制.

主要方法:

运用了正位鼠MNU和异位鼠MB-49模型来评估抗瘤功效.
在BALB/c和SCID小鼠中进行了安全评估.
分析了免疫反应,包括IFN-β释放,髓状细胞重编程,表观遗传修饰和单细胞代谢.

主要成果:

与野生型BCG (BCG-WT) 相比,BCG-disA-OE在两种测试的动物模型中都显示出更高的抗瘤疗效.
与BCG-WT相比,BCG-disA-OE在小鼠中表现出减少的增殖和较低的致死率.
BCG-disA-OE增强了IFN-β的释放,促进了类似M1的巨细胞两极分化,诱导了表观遗传变化,并将单细胞代谢转向糖解.

结论:

过度表达的刺痛激素c-di-AMP增强了BCG在膀癌的抗瘤特性.
修改BCG以释放像STING激动剂这样的促炎分子为改善膀癌治疗结果提供了一个有希望的策略.

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