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评估肺癌翻译组来源的新抗原肽疫苗的抗肿瘤作用。

Evaluation of the antitumor effect of neoantigen peptide vaccines derived from the translatome of lung cancer.

机构信息

Shengli Clinical Medical College, Fujian Medical University, No. 134 East Street, Fuzhou City, 350001, Fujian Province, China.

Department of Respiratory Medicine and Critical Care Medicine, Fujian Provincial Hospital, No. 134 East Street, Fuzhou, 350001, China.

出版信息

Cancer Immunol Immunother. 2024 May 14;73(7):129. doi: 10.1007/s00262-024-03670-0.

Abstract

Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.

摘要

新出现的证据表明,肿瘤特异性新生抗原是癌症免疫治疗的理想靶点。然而,如何基于翻译组数据来预测肿瘤新生抗原仍然不清楚。通过从 LLC 细胞中提取核糖体-新生链复合物(RNC),然后提取 RNC-mRNA、进行 RNC-mRNA 测序和全面的生物信息学分析,我们成功地鉴定了在细胞中转录组中发生翻译并出现突变的蛋白质。随后,通过高亲和力与主要组织相容性复合体(MHC)之间的相互作用分析了新抗原的识别。通过酶联免疫斑点分析(ELISpot)分析了 neoantigens 的免疫原性。最后,在小鼠体内实验中评估了源自肺癌翻译组的 neoantigen 肽对肺癌的抗肿瘤作用。结果表明,从 LLC 细胞的翻译组数据中鉴定和合成了十个 neoantigen 肽;其中 8 个 neoantigens 具有很强的免疫原性。neoantigen 肽疫苗组表现出明显的肿瘤生长抑制作用。总之,源自肺癌翻译组的 neoantigen 肽疫苗表现出明显的肿瘤生长抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4879/11093939/b72595887843/262_2024_3670_Fig1_HTML.jpg

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