基于新抗原的癌症疫苗正在成为有前途的肿瘤疗法，但免疫原性的增强可以进一步改善治疗结果。在这里，我们证明将不同的肽新抗原锚定在皮下施用的血清外泌体上可促进淋巴结归巢和树突状细胞摄取，从而导致体外和体内抗原性显着增强。锚定黑色素瘤肽新抗原的外泌体增强了体外和体内 T 细胞反应的强度和广度，并且在更大程度上增强了 CD8 T 细胞反应。在患有黑色素瘤和结肠癌的小鼠中，血清外泌体上不同肽新抗原的同时修饰诱导了有效的肿瘤抑制和新抗原特异性免疫反应。通过将新抗原染色的血清外泌体疫苗与程序性细胞死亡蛋白 1 (PD-1) 抗体相结合，在患有结肠癌的小鼠中实现了完全根除肿瘤和可持续的免疫记忆。重要的是，载有肽新抗原的人血清外泌体在人结肠癌 3D 多细胞球体中引起显着的肿瘤生长迟缓和免疫反应。我们的研究表明，血清外泌体可直接体内定位，增加树突状细胞的摄取并增强抗原肽的免疫原性，从而为基于肽抗原的个性化免疫治疗提供通用的递送工具。版权所有 © 2023 美国基因与细胞治疗学会。由爱思唯尔公司出版。保留所有权利。

Neoantigen-based cancer vaccines are emerging as promising tumor therapies, but enhancement of immunogenicity can further improve therapeutic outcomes. Here, we demonstrate that anchoring different peptide neoantigens on subcutaneously administered serum exosomes promote lymph node homing and dendritic cell uptake, resulting in significantly enhanced antigenicity in vitro and in vivo. Exosomes anchoring of melanoma peptide neoantigens augmented the magnitude and breadth of T cell response in vitro and in vivo, to a greater extent with CD8+ T cell responses. Simultaneous decoration of different peptide neoantigens on serum exosomes induced potent tumor suppression and neoantigen-specific immune responses in mice with melanoma and colon cancer. Complete tumor eradication and sustainable immunological memory were achieved with neoantigen-painted serum exosome vaccines in combination with programmed cell death protein-1 (PD-1) antibodies in mice with colon cancer. Importantly, human serum exosomes loaded with peptide neoantigens elicited significant tumor growth retardation and immune responses in human colon cancer 3D multicellular spheroids. Our study demonstrates that serum exosomes direct in vivo localization, increase dendritic cell uptake and enhance the immunogenicity of antigenic peptides, and thus provides a general delivery tool for peptide antigen-based personalized immunotherapy.Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.