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自组装肽表位作为抗癌疫苗接种的新型平台

Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination.

作者信息

Rad-Malekshahi Mazda, Fransen Marieke F, Krawczyk Małgorzata, Mansourian Mercedeh, Bourajjaj Meriem, Chen Jian, Ossendorp Ferry, Hennink Wim E, Mastrobattista Enrico, Amidi Maryam

机构信息

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands.

Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran, Iran.

出版信息

Mol Pharm. 2017 May 1;14(5):1482-1493. doi: 10.1021/acs.molpharmaceut.6b01003. Epub 2017 Jan 27.

Abstract

The aim of the present study was to improve the immunogenicity of peptide epitope vaccines using novel nanocarriers based on self-assembling materials. Several studies demonstrated that peptide antigens in nanoparticulate form induce stronger immune responses than their soluble forms. However, several issues such as poor loading and risk of inducing T cell anergy due to premature release of antigenic epitopes have challenged the clinical success of such systems. In the present study, we developed two vaccine delivery systems by appending a self-assembling peptide (Ac-AAVVLLLW-COOH) or a thermosensitive polymer poly(N-isopropylacrylamide (pNIPAm) to the N-terminus of different peptide antigens (OVA, HPV-E7) to generate self-assembling peptide epitopes (SAPEs). The obtained results showed that the SAPEs were able to form nanostructures with a diameter from 20 to 200 nm. The SAPEs adjuvanted with CpG induced and expanded antigen-specific CD8 T cells in mice. Furthermore, tumor-bearing mice vaccinated with SAPEs harboring the HPV E7 peptide showed a delayed tumor growth and an increased survival compared to sham-treated mice. In conclusion, self-assembling peptide based systems increase the immunogenicity of peptide epitope vaccines and therefore warrants further development toward clinical use.

摘要

本研究的目的是使用基于自组装材料的新型纳米载体来提高肽表位疫苗的免疫原性。多项研究表明,纳米颗粒形式的肽抗原比其可溶性形式能诱导更强的免疫反应。然而,诸如负载率低以及由于抗原表位过早释放而诱导T细胞无反应性的风险等若干问题,对这类系统的临床成功构成了挑战。在本研究中,我们通过将一种自组装肽(Ac-AAVVLLLW-COOH)或一种热敏聚合物聚(N-异丙基丙烯酰胺)(pNIPAm)连接到不同肽抗原(OVA、HPV-E7)的N端,开发了两种疫苗递送系统,以生成自组装肽表位(SAPE)。所得结果表明,SAPE能够形成直径为20至200 nm的纳米结构。用CpG佐剂的SAPE在小鼠体内诱导并扩增了抗原特异性CD8 T细胞。此外,与假处理小鼠相比,接种含有HPV E7肽的SAPE的荷瘤小鼠肿瘤生长延迟且生存期延长。总之,基于自组装肽的系统提高了肽表位疫苗的免疫原性,因此值得进一步开展临床应用研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7564/5415879/7d14ed89dd67/mp-2016-010034_0006.jpg

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