细胞外矩阵支架辅助瘤疫苗诱导瘤回归和长期免疫记忆
Sanjay Pal1, Rohan Chaudhari1,2, Iris Baurceanu1
1Cancer Biomaterials Engineering Section, Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.
Advanced materials (Deerfield Beach, Fla.)
|February 1, 2024
概括
可注射细胞外基质 (ECM) 支架通过延长抗原暴露和促进细胞毒性T细胞免疫力来增强癌症疫苗免疫疗法. 这种方法有效治疗已建立的瘤,并产生长期免疫记忆.
科学领域:
- 生物材料科学 生物材料科学
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 可注射支架对于癌症疫苗免疫疗法至关重要,影响释放动力学和免疫反应.
- 来自脱细胞化组织的细胞外基质 (ECM) 支架促进有利于愈合的炎症反应,增强局部癌症免疫监测.
- 设计一种ECM支架辅助的癌症疫苗的目的是保持有利于治疗的免疫微环境.
研究的目的:
- 设计一种ECM支架辅助的治疗性癌症疫苗,使用脱细胞化小肠子粘膜 (SIS).
- 选免疫刺激辅助剂与SIS ECM支架一起提供.
- 评估疫苗在诱导细胞毒性免疫和治疗结果方面的有效性.
主要方法:
- 脱细胞化小肠子粘膜 (SIS) 用于创建ECM支架.
- 各种免疫刺激辅助剂被选为与SIS ECM支架一起配送.
- 配方疫苗的疗效在EG-7OVA淋巴瘤的小鼠模型中进行了评估,评估瘤治愈率,免疫细胞反应 (CD8+ T细胞) 和免疫记忆.
主要成果:
- 鉴定出STING通路激动剂周期性di-AMP是ECM支架疫苗中最有效的辅助剂.
- 该SIS-ECM支架疫苗诱导了强大的细胞毒性免疫力,而不影响IL-4介导的愈合途径.
- 该疫苗治愈了50-75%的老鼠确定的EG-7OVA淋巴瘤瘤,显著超过可溶性疫苗.
- SIS-ECM支架辅助疫苗接种导致长时间的抗原暴露,依赖CD8+细胞毒性T细胞,并产生长期的抗原特异性免疫记忆.
结论:
- 对于提高癌症疫苗疗效而言,ECM支架是有前途的交付工具.
- 设计的SIS-ECM支架疫苗促进抗瘤免疫力,同时支持有利于愈合的免疫反应.
- 该策略通过利用组织重建特征,为癌症免疫疗法提供了一种新的方法.
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