Neo-intline: integrated pipeline enables neoantigen design through the in-silico presentation of T-cell epitope  

作　　者：Bingyu Li Ping Jing Genhui Zheng Chenyu Pi Lu Zhang Zuojing Yin Lijun Xu Jingxuan Qiu Hua Gu Tianyi Qiu Jianmin Fang 

机构地区：[1]Laboratory of Molecular Medicine,Shanghai Key Laboratory of Signaling and Disease Research,School of Life Sciences and Technology,Tongji Hospital,Tongji University Suzhou Institute,Tongji University,Shanghai,China [2]School of Basic Medical Sciences,Henan University of Science and Technology,Luoyang,Henan,China [3]Institute of Clinical Science,Zhongshan Hospital,Fudan University,Shanghai,China [4]Oden Institute for Computational Engineering and Sciences(ICES),University of Texas at Austin,Austin,TX,USA [5]School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai,China [6]Shanghai Institute of Infectious Disease and Biosecurity,Fudan University,Shanghai,200032,China

出　　处：《Signal Transduction and Targeted Therapy》2023年第11期5417-5428,共12页信号转导与靶向治疗（英文）

基　　金：We wish to thank all members of our laboratory for their helpful suggestions and support.This study was supported by grants from the National Natural Science Foundation of China(32370697,31900483);the Shanghai Sailing Program(19YF1441100);the Shanghai Science&Technology Basic Research Program(18JC1414400);the Key Science and Technology Program of Henan Province(212102310872).

摘　　要：Neoantigen vaccines are one of the most effective immunotherapies for personalized tumour treatment.The current immunogen design of neoantigen vaccines is usually based on whole-genome sequencing(WGS)and bioinformatics prediction that focuses on the prediction of binding affinity between peptide and MHC molecules,ignoring other peptide-presenting related steps.This may result in a gap between high prediction accuracy and relatively low clinical effectiveness.In this study,we designed an integrated in-silico pipeline,Neo-intline,which started from the SNPs and indels of the tumour samples to simulate the presentation process of peptides in-vivo through an integrated calculation model.Validation on the benchmark dataset of TESLA and clinically validated neoantigens illustrated that neo-intline could outperform current state-of-the-art tools on both sample level and melanoma level.Furthermore,by taking the mouse melanoma model as an example,we verified the effectiveness of 20 neoantigens,including 10 MHC-I and 10 MHC-II peptides.The in-vitro and in-vivo experiments showed that both peptides predicted by Neo-intline could recruit corresponding CD4^(+)T cells and CD8^(+)T cells to induce a T-cell-mediated cellular immune response.Moreover,although the therapeutic effect of neoantigen vaccines alone is not sufficient,combinations with other specific therapies,such as broad-spectrum immune-enhanced adjuvants of granulocyte-macrophage colony-stimulating factor(GM-CSF)and polyinosinic-polycytidylic acid(poly(I:C)),or immune checkpoint inhibitors,such as PD-1/PD-L1 antibodies,can illustrate significant anticancer effects on melanoma.Neo-intline can be used as a benchmark process for the design and screening of immunogenic targets for neoantigen vaccines.

关 键 词：MELANOMA PREDICTION enable 

分 类 号：R730.51[医药卫生—肿瘤]