fcrn引导的抗原运输增强了癌症疫苗的效力。

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2025-01-03 DOI:10.1007/s00262-024-03888-y
Mengyu Hong, Muziying Liu, Fang Zhu, Dan Zhao, Guilai Liu, Tiyun Han, Caiyi Fei, Weihong Zeng, Shi Chen, Qiqin Wu, Bofeng Li, Songquan Wu, Yuhua Shang, Huan Ma, Shoubing Zhou, Shi Xu, Tengchuan Jin
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引用次数: 0

摘要

肿瘤疫苗的开发是癌症治疗学研究的一个重要焦点。然而,肿瘤疫苗抗原呈递的效率仍然不够理想。我们介绍了一个创新的mrna -脂质纳米粒子平台,旨在表达与新生儿Fc受体(FcRn)的跨膜结构域和细胞质尾部融合的肿瘤抗原表位。这种新颖的设计利用FcRn运输信号来指导表位-FcRn融合到内溶酶体降解,从而产生能够引发靶向T细胞反应和建立免疫记忆的表位。fcrn导向的表位呈递增强MHC I类和II类抗原呈递,从而强有力地诱导CD4+和CD8+ T细胞应答,从而在临床前小鼠模型中转化为抑制肿瘤生长和延长生存期。总之,有意将FcRn转运信号纳入疫苗设计可显著增强T细胞应答,强调了这种新策略在提高肿瘤疫苗疗效方面的前景。
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FcRn-guided antigen trafficking enhances cancer vaccine efficacy.

The development of tumor vaccines represents a significant focus within cancer therapeutics research. Nonetheless, the efficiency of antigen presentation in tumor vaccine remains suboptimal. We introduce an innovative mRNA-lipid nanoparticle platform designed to express tumor antigenic epitopes fused with the transmembrane domain and cytoplasmic tail of the neonatal Fc receptor (FcRn). This novel design exploits FcRn trafficking signals to direct the epitope-FcRn fusion toward endolysosomal degradation, thereby generating epitopes capable of eliciting targeted T cell responses and establishing immune memory. The FcRn-directed presentation of epitopes enhances MHC class I and II antigen presentation, thereby robustly inducing CD4+ and CD8+ T cell responses, which translates to the inhibition of tumor growth and extension of survival in preclinical mouse models. In summary, the deliberate incorporation of FcRn trafficking signals into vaccine design markedly boosts T cell responses, underscoring the promise of this novel strategy in advancing the efficacy of tumor vaccines.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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