已知成熟红细胞缺乏主要组织相容性复合体 (MHC) 蛋白。然而，偶尔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，我们设计了仅与融合蛋白缀合的红细胞，该融合蛋白由与 MHC I 类 (MHC-I) 蛋白连接的抗原肽组成，称为 MHC-I-Ery。修饰有源自人乳头瘤病毒 (HPV) 16 癌蛋白 E6/E7 的肽的修饰红细胞，可有效激活 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 单一疗法被证明可以抑制小鼠抗原阳性肿瘤的生长。这种治疗立即激活了 CD8 T 细胞并减少了脾脏中的抑制性骨髓细胞，从而产生了全身抗肿瘤活性。 MHC-I-Ery 在非人类灵长类动物中的安全性和耐受性评估进一步支持了其临床潜力。我们的结果首先证明，仅配备抗原肽-MHC-I 复合物的红细胞可以强有力地刺激免疫系统，这为推进癌症免疫治疗提出了一种新颖且有前景的方法。© 2024。作者。

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.© 2024. The Author(s).