工程化型细菌HCS1具有高免疫刺激和癌症治疗的安全性
Yujie Sun1, Yanxia Guo1, Xiaoqing Liu1
1School of Biomedical Science, Hunan University, Changsha 410082, China.
Theranostics
|November 1, 2023
概括
一种新的工程Salmonella HCS1菌株显示出增强的抗癌疗效和生物安全性. 这种减弱的细菌有效地抑制瘤并增强免疫反应,为癌症免疫治疗提供了一个有前途的新选择.
科学领域:
- 在瘤学瘤学.
- 微生物学 微生物学
- 免疫治疗是一种免疫疗法.
背景情况:
- 减弱型沙门氏菌 typhimurium VNP20009在癌症治疗中表现出潜力,但在有效性和安全性方面面临限制.
- 在临床前模型中,缺乏瓜诺辛5'-二酸盐-3'-二酸盐 (ppGpp) 合成的沙门氏菌株提供了更好的生物安全性和抗癌活性.
- 结合VNP20009和ppGpp缺乏的沙门氏菌的好处,可以推进菌性细菌治疗.
研究的目的:
- 通过将ppGpp缺陷整合到VNP20009.9中来设计一种新的沙门氏菌株,HCS1.
- 评估HCS1菌株的体外细胞毒性和体内抗瘤活性.
- 研究HCS1在瘤微环境中的免疫调节作用.
主要方法:
- 在VNP20009中通过删除relA和spoT基因来创建HCS1菌株,以实现ppGpp缺乏.
- 实验室试验评估了HCS1对癌细胞的侵入性和细胞毒性.
- 在携带瘤的小鼠体内研究评估了HCS1治疗后的抗瘤疗效,存活率和免疫反应.
主要成果:
- 与VNP20009.9相比,HCS1在体外表现出明显较低的侵入性和细胞毒性.
- 在小鼠中,静脉注射HCS1导致了强大的瘤抑制,增加了生存时间和更高的治愈率.
- HCS1治疗增加了促炎性细胞因子,缓解了瘤微环境免疫抑制,并招募了免疫细胞,增强了免疫激活.
结论:
- 工程Salmonella HCS1菌株表现出增强的生物安全性和强大的抗瘤活性.
- HCS1有效地重塑瘤微环境以促进抗瘤免疫力.
- HCS1代表了未来癌症免疫治疗中临床应用的有希望的候选人.
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