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突变组工程化RNA免疫疗法:迈向以患者为中心的肿瘤疫苗接种

Mutanome Engineered RNA Immunotherapy: Towards Patient-Centered Tumor Vaccination.

作者信息

Vormehr Mathias, Schrörs Barbara, Boegel Sebastian, Löwer Martin, Türeci Özlem, Sahin Ugur

机构信息

Research Center for Immunotherapy (FZI), Langenbeckstr. 1, Building 708, 55131 Mainz, Germany; Biopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, 55131 Mainz, Germany.

TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, Freiligrathstr. 12, 55131 Mainz, Germany.

出版信息

J Immunol Res. 2015;2015:595363. doi: 10.1155/2015/595363. Epub 2015 Dec 30.

Abstract

Advances in nucleic acid sequencing technologies have revolutionized the field of genomics, allowing the efficient targeting of mutated neoantigens for personalized cancer vaccination. Due to their absence during negative selection of T cells and their lack of expression in healthy tissue, tumor mutations are considered as optimal targets for cancer immunotherapy. Preclinical and early clinical data suggest that synthetic mRNA can serve as potent drug format allowing the cost efficient production of highly efficient vaccines in a timely manner. In this review, we describe a process, which integrates next generation sequencing based cancer mutanome mapping, in silico target selection and prioritization approaches, and mRNA vaccine manufacturing and delivery into a process we refer to as MERIT (mutanome engineered RNA immunotherapy).

摘要

核酸测序技术的进步彻底改变了基因组学领域,使针对突变新抗原进行个性化癌症疫苗接种成为可能。由于肿瘤突变在T细胞阴性选择过程中不存在,且在健康组织中不表达,因此被认为是癌症免疫治疗的理想靶点。临床前和早期临床数据表明,合成mRNA可作为一种有效的药物形式,能够及时以具有成本效益的方式生产高效疫苗。在本综述中,我们描述了一个过程,该过程将基于下一代测序的癌症突变组图谱绘制、计算机靶点选择和优先级排序方法,以及mRNA疫苗的制造和递送整合到一个我们称为MERIT(突变组工程化RNA免疫疗法)的过程中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f020/4710911/8c13baea3e4c/JIR2015-595363.001.jpg

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