Hongjian Tian , Wenfeng Zeng , Zihao Wang , Siqi Li , Wenjing Wei , Shanshan Li , Xiaozhe Yin , Wenjing Na , Youwang Wang , Kai Song , Ping Zhu , Wei Liang
{"title":"P-Pev:由肿瘤细胞外囊泡转化的胶束样复合物,用于个性化治疗性肿瘤疫苗","authors":"Hongjian Tian , Wenfeng Zeng , Zihao Wang , Siqi Li , Wenjing Wei , Shanshan Li , Xiaozhe Yin , Wenjing Na , Youwang Wang , Kai Song , Ping Zhu , Wei Liang","doi":"10.1016/j.biomaterials.2025.123333","DOIUrl":null,"url":null,"abstract":"<div><div>The clinical benefits of personalized therapeutic tumor vaccines are mainly challenged by the need to identify immunogenic neoantigens promptly, given the rapid pace of tumor mutations. An increasing body of literature addresses the potential of tumor-derived extracellular vesicles (TEVs) as an anti-tumor “cell-free” vaccine due to their substantial presence of neoantigens. However, their immunosuppression and limited presentation efficiency of dendritic cells (DCs) restrict their further application. Here, we have developed a novel tumor-personalized vaccine, termed P-Pev, based on remodeled TEVs by polymeric surfactant polyethylene glycol-phosphatidyleolamine (PEG-PE) and adjuvant monophosphoryl lipid A (MPLA). Our results show that PEG-PE transforms TEVs into micelle-like complexes by disrupting the original structure, facilitating antigens delivery to the cytoplasm, and cross-presentation by DCs. P-Pev particularly prevents the immunosuppressive impacts of TEVs on the ability of DCs to prime CD8<sup>+</sup> T cells and eliminates the potency of TEVs to promote lung metastasis through their membrane-bound PD-L1. Finally, the P-Pev effectively induces neoantigen-specific cytotoxic T lymphocytes (CTLs) responses and exhibits excellent therapeutic effects in various murine tumor models. Also, the P-Pev induces neoantigen-specific antibodies, suggesting the involvement of humoral immunity in its anti-tumor effects. More importantly, it has been shown that P-Pev prepared by mutated tumor cells can retard these mutated tumor cell-established syngeneic tumors better than P-Pev prepared by original tumor cells, indicating the feasibility that leverages TEVs to prepare personalized tumor vaccines, and it is synergistically enhanced by PD-1 mAb combination. Collectively, we present a general strategy that offers a streamlined, cost-effective, and time-consuming approach to preparing personalized therapeutic tumor vaccines.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123333"},"PeriodicalIF":12.8000,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"P-Pev: micelle-like complexes transformed from tumor extracellular vesicles by PEG-PE for personalized therapeutic tumor vaccine\",\"authors\":\"Hongjian Tian , Wenfeng Zeng , Zihao Wang , Siqi Li , Wenjing Wei , Shanshan Li , Xiaozhe Yin , Wenjing Na , Youwang Wang , Kai Song , Ping Zhu , Wei Liang\",\"doi\":\"10.1016/j.biomaterials.2025.123333\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The clinical benefits of personalized therapeutic tumor vaccines are mainly challenged by the need to identify immunogenic neoantigens promptly, given the rapid pace of tumor mutations. An increasing body of literature addresses the potential of tumor-derived extracellular vesicles (TEVs) as an anti-tumor “cell-free” vaccine due to their substantial presence of neoantigens. However, their immunosuppression and limited presentation efficiency of dendritic cells (DCs) restrict their further application. Here, we have developed a novel tumor-personalized vaccine, termed P-Pev, based on remodeled TEVs by polymeric surfactant polyethylene glycol-phosphatidyleolamine (PEG-PE) and adjuvant monophosphoryl lipid A (MPLA). Our results show that PEG-PE transforms TEVs into micelle-like complexes by disrupting the original structure, facilitating antigens delivery to the cytoplasm, and cross-presentation by DCs. P-Pev particularly prevents the immunosuppressive impacts of TEVs on the ability of DCs to prime CD8<sup>+</sup> T cells and eliminates the potency of TEVs to promote lung metastasis through their membrane-bound PD-L1. Finally, the P-Pev effectively induces neoantigen-specific cytotoxic T lymphocytes (CTLs) responses and exhibits excellent therapeutic effects in various murine tumor models. Also, the P-Pev induces neoantigen-specific antibodies, suggesting the involvement of humoral immunity in its anti-tumor effects. More importantly, it has been shown that P-Pev prepared by mutated tumor cells can retard these mutated tumor cell-established syngeneic tumors better than P-Pev prepared by original tumor cells, indicating the feasibility that leverages TEVs to prepare personalized tumor vaccines, and it is synergistically enhanced by PD-1 mAb combination. Collectively, we present a general strategy that offers a streamlined, cost-effective, and time-consuming approach to preparing personalized therapeutic tumor vaccines.</div></div>\",\"PeriodicalId\":254,\"journal\":{\"name\":\"Biomaterials\",\"volume\":\"321 \",\"pages\":\"Article 123333\"},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2025-04-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomaterials\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0142961225002522\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0142961225002522","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
P-Pev: micelle-like complexes transformed from tumor extracellular vesicles by PEG-PE for personalized therapeutic tumor vaccine
The clinical benefits of personalized therapeutic tumor vaccines are mainly challenged by the need to identify immunogenic neoantigens promptly, given the rapid pace of tumor mutations. An increasing body of literature addresses the potential of tumor-derived extracellular vesicles (TEVs) as an anti-tumor “cell-free” vaccine due to their substantial presence of neoantigens. However, their immunosuppression and limited presentation efficiency of dendritic cells (DCs) restrict their further application. Here, we have developed a novel tumor-personalized vaccine, termed P-Pev, based on remodeled TEVs by polymeric surfactant polyethylene glycol-phosphatidyleolamine (PEG-PE) and adjuvant monophosphoryl lipid A (MPLA). Our results show that PEG-PE transforms TEVs into micelle-like complexes by disrupting the original structure, facilitating antigens delivery to the cytoplasm, and cross-presentation by DCs. P-Pev particularly prevents the immunosuppressive impacts of TEVs on the ability of DCs to prime CD8+ T cells and eliminates the potency of TEVs to promote lung metastasis through their membrane-bound PD-L1. Finally, the P-Pev effectively induces neoantigen-specific cytotoxic T lymphocytes (CTLs) responses and exhibits excellent therapeutic effects in various murine tumor models. Also, the P-Pev induces neoantigen-specific antibodies, suggesting the involvement of humoral immunity in its anti-tumor effects. More importantly, it has been shown that P-Pev prepared by mutated tumor cells can retard these mutated tumor cell-established syngeneic tumors better than P-Pev prepared by original tumor cells, indicating the feasibility that leverages TEVs to prepare personalized tumor vaccines, and it is synergistically enhanced by PD-1 mAb combination. Collectively, we present a general strategy that offers a streamlined, cost-effective, and time-consuming approach to preparing personalized therapeutic tumor vaccines.
期刊介绍:
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.