Yuehua Liu, Xiaoqian Nie, Xingyun Yao, Huafeng Shou, Yang Yuan, Yun Ge, Xiangmin Tong, Hsiang-Ying Lee, Xiaofei Gao
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引用次数: 0
摘要
众所周知,成熟的红细胞缺乏主要组织相容性复合体(MHC)蛋白。不过,偶尔也有报道称红细胞上存在 MHC 分子,但没有明确的功能。在这项研究中,我们设计了仅与一种融合蛋白结合的红细胞,这种融合蛋白由与 MHC I 类蛋白质(MHC-I)相连的抗原肽组成,被称为 MHC-I-Ery。经修饰的红细胞上装饰有来自人类乳头瘤病毒(HPV)16 肿瘤蛋白 E6/E7 的多肽,能有效激活 HPV16+ 宫颈癌患者外周血单核细胞(PBMC)中的抗原特异性 CD8+ T 细胞。此外,MHC-I-Ery 单药疗法还能抑制抗原阳性肿瘤在小鼠体内的生长。这种疗法能立即激活 CD8+ T 细胞,减少脾脏中的抑制性髓细胞,从而产生全身抗肿瘤活性。MHC-I-Ery在非人灵长类动物中的安全性和耐受性评估进一步证实了它的临床潜力。我们的研究结果首次证明了红细胞仅配备抗原肽-MHC-I 复合物就能强有力地刺激免疫系统,为推进癌症免疫疗法提供了一种新颖而有前景的方法。
Developing an erythrocyte‒MHC-I conjugate for cancer treatment.
Mature erythrocytes are known to lack major histocompatibility complex (MHC) proteins. However, the presence of MHC molecules on erythrocytes has been occasionally reported, though without a defined function. In this study, we designed erythrocyte conjugated solely with a fusion protein consisting of an antigenic peptide linked to MHC class I (MHC-I) protein, termed MHC-I‒Ery. The modified erythrocyte, decorated with the peptide derived from human papillomavirus (HPV) 16 oncoprotein E6/E7, effectively activated antigen-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from HPV16+ cervical cancer patients. Additionally, MHC-I‒Ery monotherapy was shown to inhibit antigen-positive tumor growth in mice. This treatment immediately activated CD8+ T cells and reduced suppressive myeloid cells in the spleen, leading to systemic anti-tumor activity. Safety and tolerability evaluations of MHC-I‒Ery in non-human primates further supported its clinical potential. Our results first demonstrated that erythrocytes equipped solely with antigen peptide‒MHC-I complexes can robustly stimulate the immune system, suggesting a novel and promising approach for advancing cancer immunotherapy.
Cell DiscoveryBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍:
Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research.
Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals.
In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.