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

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Hongjian Tian , Wenfeng Zeng , Zihao Wang , Siqi Li , Wenjing Wei , Shanshan Li , Xiaozhe Yin , Wenjing Na , Youwang Wang , Kai Song , Ping Zhu , Wei Liang
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引用次数: 0

摘要

鉴于肿瘤突变的快速发展,个性化治疗性肿瘤疫苗的临床效益主要受到需要及时识别免疫原性新抗原的挑战。越来越多的文献指出肿瘤源性细胞外囊泡(TEVs)作为抗肿瘤“无细胞”疫苗的潜力,因为它们大量存在新抗原。然而,它们的免疫抑制和树突状细胞的呈递效率有限限制了它们的进一步应用。在这里,我们开发了一种新的肿瘤个性化疫苗,称为P-Pev,基于聚合表面活性剂聚乙二醇-磷脂酰聚胺(PEG-PE)和佐剂单磷脂酰脂质a (MPLA)重塑的tev。我们的研究结果表明,PEG-PE通过破坏tev的原始结构,促进抗原向细胞质的传递和dc的交叉呈递,将tev转化为胶束样复合物。P-Pev特别阻止了tev对dc启动CD8+ T细胞能力的免疫抑制作用,并消除了tev通过其膜结合的PD-L1促进肺转移的效力。最后,P-Pev可有效诱导新抗原特异性细胞毒性T淋巴细胞(ctl)反应,并在多种小鼠肿瘤模型中表现出优异的治疗效果。此外,P-Pev诱导新抗原特异性抗体,提示其抗肿瘤作用涉及体液免疫。更重要的是,突变肿瘤细胞制备的P-Pev比原始肿瘤细胞制备的P-Pev更能延缓这些突变肿瘤细胞建立的同基因肿瘤,这表明利用tev制备个性化肿瘤疫苗的可行性,并且与PD-1 mAb联合可协同增强tev。总的来说,我们提出了一种总体策略,提供了一种简化的、具有成本效益的、耗时的方法来制备个性化的治疗性肿瘤疫苗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
Biomaterials
Biomaterials 工程技术-材料科学:生物材料
CiteScore
26.00
自引率
2.90%
发文量
565
审稿时长
46 days
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.
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