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病例报告:叶状肿瘤患者肺部转移灶经含肽新抗原纳米疫苗治疗后达到病理完全缓解

Case Report: Pathological Complete Response in a Lung Metastasis of Phyllodes Tumor Patient Following Treatment Containing Peptide Neoantigen Nano-Vaccine.

作者信息

Sha Huizi, Liu Qin, Xie Li, Shao Jie, Yu Lixia, Cen Lanqi, Li Lin, Liu Fangcen, Qian Hanqing, Wei Jia, Liu Baorui

机构信息

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Department of Pathology of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

出版信息

Front Oncol. 2022 Feb 8;12:800484. doi: 10.3389/fonc.2022.800484. eCollection 2022.

Abstract

Some of the mutant peptides produced by gene mutation transcription and translation have the ability to induce specific T cells, which are called new antigens. Neoantigen-based peptide, DNA, RNA, and dendritic cell vaccines have been used in the clinic. In this paper, we describe a lung metastasis of a phyllodes tumor patient demonstrating pathological complete response following treatment containing personalized multi-epitope peptide neoantigen nano-vaccine. Based on whole-exome sequencing (WES), RNA sequencing, and new antigen prediction, several mutated peptide fragments were predicted to bind to the patient's human leukocyte antigen (HLA) allotypes, including ten peptides with high predicted binding affinity for six genes. The pulmonary metastases remained stable after the four cycles of anti-PD1 and anlotinib. After the addition of the multi-epitope peptide neoantigen nano-vaccine, the tumor began to collapse and contracture developed, accompanied by a decrease of tumor markers to normal, and complete pathological remission was achieved. With the use of the vaccination, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was used every time, and low-dose cyclophosphamide was injected every 3 weeks to improve efficacy. Peripheral blood immune monitoring demonstrated immune reactivity against a series of peptides, with the most robust post-vaccine T-cell response detected against the HLA-DRB1*0901-restricted SLC44A5 V54F peptide.

摘要

由基因突变转录和翻译产生的一些突变肽具有诱导特异性T细胞的能力,这些肽被称为新抗原。基于新抗原的肽、DNA、RNA和树突状细胞疫苗已应用于临床。在本文中,我们描述了一例叶状肿瘤患者的肺转移情况,该患者在接受含个性化多表位肽新抗原纳米疫苗的治疗后出现了病理完全缓解。基于全外显子组测序(WES)、RNA测序和新抗原预测,预测了几个突变肽片段可与患者的人类白细胞抗原(HLA)亚型结合,其中包括对六个基因具有高预测结合亲和力的十个肽。在接受四个周期的抗PD1和安罗替尼治疗后,肺转移灶保持稳定。添加多表位肽新抗原纳米疫苗后,肿瘤开始缩小并出现挛缩,同时肿瘤标志物降至正常水平,实现了病理完全缓解。每次接种疫苗时使用重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF),每3周注射低剂量环磷酰胺以提高疗效。外周血免疫监测显示对一系列肽具有免疫反应性,接种疫苗后针对HLA-DRB1*0901限制性SLC44A5 V54F肽检测到最强的T细胞反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd6a/8861377/bb2cdeb71a0c/fonc-12-800484-g001.jpg

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