基于益生菌的个性化癌症疫苗通过启动训练免疫来增强抗瘤免疫力
Zhaoxia Chen1, Tuying Yong1,2,3, Zhaohan Wei1
1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|November 27, 2023
概括
这项研究设计了一种益生菌细菌,以创建个性化癌症疫苗,诱导训练免疫和适应性抗瘤反应. 这种方法对预防瘤复发和增强癌症免疫疗法的有希望.
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:
- 癌症疫苗的目的是刺激T细胞免疫力,但面临诸如有限的抗原呈现细胞和免疫抑制瘤微环境等挑战.
- 训练有素的先天免疫是一种潜在的策略,可以增强瘤抗原特异性适应性免疫力,以提高癌症疫苗的疗效.
研究的目的:
- 开发一个个性化的癌症疫苗,通过设计一个无活化的益生菌Escherichia coli Nissle 1917来提供瘤抗原和训练有素的免疫诱导剂.
- 评估疫苗诱导受训天生的免疫,促进抗原呈现,并引起适应性抗瘤反应的能力.
主要方法:
- 工程失活了埃舍里希亚大肠杆菌尼斯尔1917以携带瘤抗原 (例如,OVA) 和β-葡萄糖.
- 在临床前模型中,对工程疫苗 (BG/OVA@EcN) 进行皮下注射.
- 评估巨细胞和树突细胞的招募,激活和随后的T细胞反应.
- 评估预防性和治疗性抗瘤疗效,包括通过自身抗原预防瘤复发.
主要成果:
- BG/OVA@EcN在注射部位积聚在巨细胞中,诱导训练免疫,增强树突细胞成熟和T细胞激活.
- 该疫苗促进了循环训练的单细胞/巨细胞的循环,导致瘤中的M1样巨细胞分化.
- BG/OVA@EcN证明了显著的预防和治疗疗效,抑制瘤生长和建立长期免疫记忆.
- 具有自身瘤抗原的疫苗有效地预防了术后瘤复发.
结论:
- 工程化益生菌细菌可以通过整合训练的先天性和适应性免疫来作为个性化癌症疫苗的平台.
- 这种策略通过增强抗原呈现和调节瘤微环境来克服传统癌症疫苗的局限性.
- 开发的癌症疫苗平台为有效的个性化癌症免疫疗法提供了可翻译的方法.
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