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基于结构依赖的免疫细胞迁移和调节的癌症免疫治疗用免疫原性物质疫苗。

Immunogenic Material Vaccine for Cancer Immunotherapy by Structure-Dependent Immune Cell Trafficking and Modulation.

机构信息

Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, P. R. China.

Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.

出版信息

Adv Mater. 2024 Jul;36(27):e2402580. doi: 10.1002/adma.202402580. Epub 2024 Apr 24.

Abstract

Inherently immunogenic materials offer enormous prospects in enhancing vaccine efficacy. However, the understanding and improving material adjuvanticity remain elusive. Herein how the structural presentation of immunopotentiators in a material governs the dynamic dialogue between innate and adaptive immunity for enhanced cancer vaccination is reported. The immunopotentiator manganese into six differing structures that resemble the architectures of two types of pathogens (spherical viruses or rod-like bacteria) is precisely manipulated. The results reveal that innate immune cells accurately sense and respond to the architectures, of which two outperformed material candidates (151 nm hollow spheres and hollow microrods with an aspect ratio of 4.5) show higher competence in creating local proinflammatory environment with promoted innate immune cell influx and stimulation on dendritic cells (DCs). In combination with viral peptides, model proteins, or cell lysate antigens, the outperformed microrod material remarkably primes antigen-specific CD8 cytolytic T cells. In prophylactic and therapeutic regimens, the microrod adjuvanted vaccines display optimal aptitude in tumor suppression in four aggressive murine tumor models, by promoting the infiltration of heterogeneous cytolytic effector cells while decreasing suppressive immunoregulatory populations in tumors. This study demonstrates that a rationally selected architecture of immunogenic materials potentially advances the clinical reality of cancer vaccination.

摘要

固有免疫原性材料在增强疫苗效力方面具有巨大的前景。然而,对材料佐剂特性的理解和改善仍然难以捉摸。本文报道了免疫佐剂在材料中的结构呈现方式如何控制固有免疫和适应性免疫之间的动态对话,以增强癌症疫苗接种的效果。本文通过精确操纵免疫佐剂锰形成六种不同的结构,使其类似于两种类型病原体(球形病毒或杆状细菌)的结构。结果表明,固有免疫细胞能够准确地感知和响应这些结构,其中两种材料候选物(151nm 空心球和纵横比为 4.5 的中空微米棒)表现出更高的能力,能够创造局部促炎环境,促进固有免疫细胞的流入和树突状细胞(DCs)的刺激。与病毒肽、模型蛋白或细胞裂解物抗原结合后,表现优异的微米棒材料能够显著引发抗原特异性 CD8 细胞毒性 T 细胞。在预防性和治疗性方案中,微米棒佐剂疫苗在四种侵袭性小鼠肿瘤模型中表现出最佳的肿瘤抑制能力,通过促进异质性细胞毒性效应细胞的浸润,同时减少肿瘤中的抑制性免疫调节细胞群。本研究表明,经过合理选择的免疫原性材料的结构有可能推动癌症疫苗接种的临床现实。

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