一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
一种在新鲜人肺癌中识别新抗原反应性 T 细胞的表型特征
英文原题：A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers.
查看英文原题
A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers.
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中文摘要
多种成功的癌症免疫疗法的一个共同主题是T细胞对肿瘤特异性突变（新抗原）的识别。快速发现此类抗原反应可能通过过继转移经工程化表达新抗原反应性T细胞受体（TCR）的T细胞来改善疗法。在此，通过对非小细胞肺癌（NSCLC）TIL（肿瘤浸润淋巴细胞）进行CITE-seq（通过测序对转录组和表位进行细胞索引）和TCR-seq，我们基于克隆型频率以及CD39蛋白和CXCL13 mRNA表达开发了一种新抗原反应性T细胞特征。通过该特征筛选所选TCR，使我们能够鉴定新抗原反应性TCR，CD8 + T细胞的成功率为45%，CD4 + T细胞为66%。由于分析的样本数量较少（4例患者），普适性仍有待检验。然而，这种方法能够快速鉴定新抗原反应性TCR，并加速用于治疗的个性化新抗原反应性T细胞的工程化。
展开英文摘要原文
A common theme across multiple successful immunotherapies for cancer is the recognition of tumor-specific mutations (neoantigens) by T cells. The rapid discovery of such antigen responses could lead to improved therapies through the adoptive transfer of T cells engineered to express neoantigen-reactive T cell receptors (TCRs).
Here, through CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and TCR-seq of non-small cell lung cancer (NSCLC) tumor-infiltrating lymphocytes (TILs), we develop a neoantigen-reactive T cell signature based on clonotype frequency and CD39 protein and CXCL13 mRNA expression. Screening of TCRs selected by the signature allows us to identify neoantigen-reactive TCRs with a success rate of 45% for CD8 + and 66% for CD4 + T cells. Because of the small number of samples analyzed (4 patients), generalizability remains to be tested.
However, this approach can enable the quick identification of neoantigen-reactive TCRs and expedite the engineering of personalized neoantigen-reactive T cells for therapy.
论文信息
- 作者
- Hanada KI、Zhao C、Gil-Hoyos R、Gartner JJ、Chow-Parmer C、Lowery FJ、Krishna S、Prickett TD
- 第一作者单位
- Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: hanada@nih.gov.United States
- 通讯作者单位
- Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jamesyang@mail.nih.gov.United States
- 文献类型
- 美国 NIH 资助研究 · 美国 NIH 院内研究
- 期刊
- Cancer cell2022 May 9
- 原文标识
- PubMed 35452604 · DOI 10.1016/j.ccell.2022.03.012
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