Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles.

IF 12.1 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-07-16 DOI:10.1016/j.ymthe.2025.07.014

Lasse Neukirch,Silke Uhrig-Schmidt,Katharina von Werthern,Alexandra Tuch,Joscha A Kraske,Yanhong Lyu,Benedicte Lenoir,Stefan B Eichmüller,Marten Meyer,Inka Zörnig,Dirk Jäger,Patrick Schmidt

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引用次数: 0

Abstract

Personalized treatment has become a realistic option for tumor patients, accelerated by significantly reduced sequencing costs of tumor genomes and advances in vaccine formulations. The druggability of cancer neo-antigens caused by individual mutations is centered in this effort. We here use an AAV-based VLP platform to compose a neo-antigen specific protein vaccine that is effective in a murine prevention and treatment setting. Furthermore, we show that CD4+ T cell responses that are provided by the AAV capsid are crucial for an effective murine melanoma treatment. To uncover the optimal composition of a peptide vaccine we de-linked MHC-II helper peptides from the capsid and formulated an efficient neo-antigen specific vaccine, which showed the independence of CD4+ T cell response from tumor sequences. The findings are supported by clinical data of neo-antigen vaccinated tumor patients. Our results punctuate on the significance of MHC-II epitopes for CD8+ T cell responses and suggest a future use of AAVLPs as neo-epitope vaccines in personalized cancer treatments.

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新抗原肿瘤疫苗接种依赖于由腺相关病毒样颗粒传递的cd4许可。

由于肿瘤基因组测序成本的显著降低和疫苗配方的进步，个性化治疗已成为肿瘤患者的一种现实选择。由个体突变引起的癌症新抗原的可药物性集中在这一努力中。我们在此使用基于aav的VLP平台合成一种新抗原特异性蛋白疫苗，该疫苗在小鼠预防和治疗环境中有效。此外，我们发现由AAV衣壳提供的CD4+ T细胞反应对于有效治疗小鼠黑色素瘤至关重要。为了揭示肽疫苗的最佳组成，我们从衣壳上脱联MHC-II辅助肽，并制定了一种高效的新抗原特异性疫苗，该疫苗显示CD4+ T细胞应答与肿瘤序列无关。新抗原免疫肿瘤患者的临床资料支持了这一发现。我们的研究结果强调了MHC-II表位对CD8+ T细胞反应的重要性，并提示未来将AAVLPs作为新表位疫苗用于个性化癌症治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.