肿瘤新抗原mRNA疫苗在加速审批的背景下,肿瘤突变抗原的研究价值越来越大,为此,我们通过文献挖掘,为读者整理了各种肿瘤的已验证肿瘤突变抗原清单,我们将陆续发布。
我们从310篇文献中,整理出了2384种结肠癌中高表达的抗原肽。筛选出能激活T细胞活性的共有15种,详情如下:
抗原肽 | 抗原蛋白 | 呈递抗原的HLA | 验证文章 |
---|---|---|---|
VNRWTRRQVILCETCLIVSSVKDSL | PH domain leucine-rich repeat-containing protein phosphatase 1 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
VKKPHRYRPGTVTLREIRRYQKSTE | Histone H3.3 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
RHRYLSHLPLTCKFSICELALQPPV | RING finger protein 10 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
PILKEIVEMLFSHGLVKVLFATETF | Helicase SKI2W | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
MTEYKLVVVGADGVGKSALTIQLI | GTPase KRas | HLA-C*08:02 | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
LYCESVHNF | Prostatic acid phosphatase | HLA-A*24:02 | Prostatic acid phosphatase as a target molecule in specific immunotherapy for patients with nonprostate adenocarcinoma. J Immunother 2005 |
KTLGIKYFSMTEVDRLGIGK | Arginase-1 | HLA class I | Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial. Front Immunol 2022 |
GDRFCLGQLSNAHRT | SMAD4 | HLA-A*02:01 | T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes. Gut 2017 |
GDRFCLGQLSNAHRT | SMAD4 | HLA-A*02:01 | T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes. Gut 2017 |
FVTQKRMEHFYLSFYTAEQLVYLST | E3 ubiquitin-protein ligase RNF213 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
EESNLSFLKELLVRINRLDLLITYL | Caspase-8 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
DVDPGEHYILKTLGIKYFSM | Arginase-1 | HLA class I | Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors – A phase I trial. Front Immunol 2022 |
DPDCVDRLLQCTQQAVPLFSKNVHS | Apoptosis inhibitor 5 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
DLSIRELVHRILLVAASYSAVTRFI | Gamma-tubulin complex component 2 | HLA class I | Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015 |
CLGQLSNA | SMAD4 | HLA-A*02:01 | T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes. Gut 2017 |
上述清单中抗原特异性T细胞的检测,需要抗原肽MHC荧光四聚体标记细胞,而后通过流式技术检测或分选细胞,我们可以提供定制生产 (定制咨询请扫描本页右侧联系人二维码)。
肿瘤突变抗原清单使用方法:
肿瘤微环境研究:
检测肿瘤浸润淋巴细胞中,肿瘤抗原特异性淋巴细胞的数量实现。具体方式是:根据清单内容,将抗原肽和HLA合成为抗原肽MHC复合物荧光四聚体,通过流式细胞检测方法,检测肿瘤浸润淋巴细胞的含量。
肿瘤免疫细胞的全身分布:
通过检测外周血中肿瘤抗原特异性淋巴细胞的数量实现。具体方法同上。
过继性肿瘤免疫细胞治疗:
使用清单中抗原肽,刺激淋巴细胞,而后使用抗原肽MHC复合物荧光四聚体或磁珠四聚体,通过流式分选或磁珠分选细胞,经体外细胞增殖后,回输体内,评估肿瘤抑制效果。
肿瘤抗原特异性TCR测序:
通过肿瘤浸润淋巴细胞、或外周血淋巴细胞,通过分选后进行单细胞TCR测序,获得抗原特异性T细胞的TCR序列,进一步进行TCR-T疗法研究。
肿瘤疫苗片段筛选:
综合上述过程,获得具有激活T细胞杀伤肿瘤细胞的经验证抗原肽MHC复合物,用于肿瘤疫苗构建。