通过工程光合作用细菌和衍生外膜囊泡重定向抗原,用于增强癌症免疫疗法
Dandan Han1,2,3, Fei Wang2,3, Yichuan Ma1
1College of Chemistry & Materials Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding 071002, China.
ACS nano
|October 2, 2023
概括
工程合成光合作用细菌捕获瘤抗原并将其传递给淋巴结,增强对癌症的免疫反应. 这种方法有效地抑制了瘤转移和复发,为新的癌症疫苗铺平了道路.
科学领域:
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
- 在瘤学瘤学.
背景情况:
- 瘤微环境 (TME) 是免疫抑制的,阻碍了有效的癌症免疫疗法.
- 瘤中的抗原呈现细胞 (APC) 功能受损,限制了抗癌免疫反应.
- 周组织中的免疫细胞保持正常功能,这表明治疗向的潜力.
研究的目的:
- 开发一种新的策略,通过重定向瘤抗原来增强癌症免疫疗法.
- 利用工程光合作用细菌 (PSB) 和它们的外膜囊泡 (OMVs) 来改善抗原传递.
- 克服免疫抑制药物TME所带来的局限性.
主要方法:
- 人工合成光合作用细菌 (PSB-MAL) 用maleimide进行了修改.
- 近红外 (NIR) 激光介导光热疗法 (PTT) 诱导癌细胞死亡和抗原释放.
- 通过NIR光战术,PSB-MAL将释放的瘤抗原运送到瘤外围.
- 由PSB-MAL衍生的OMV (OMVPSB-MAL) 捕获并将抗原传递到瘤排水淋巴结 (TDLNs).
主要成果:
- 在NIR激光暴露下,PSB-MAL有效地捕获并将瘤抗原运送到瘤外围.
- OMVPSB-MAL在TDLN中促进了成熟的APC增强抗原呈现.
- 观察到细胞毒性T淋巴细胞 (CTLs) 透到瘤中的增加.
- 在黑色素瘤和乳腺癌模型中实现了强大的抗瘤免疫反应,抑制转移,减少瘤复发.
结论:
- 工程PSB及其OMV可以用于重定向瘤抗原,以增强癌症免疫疗法.
- 这种方法通过促进TDLN中的抗原呈现来克服TME诱导的免疫抑制.
- 该战略显示,在开发有效的癌症疫苗和个性化癌症治疗策略方面,有很大的前景.
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