Laboratory and Clinical studies on T-cells recognizing NSCLC

T 细胞识别 NSCLC 的实验室和临床研究

• 批准号: 10926258
• 负责人: James C Yang
• 金额: $ 46.44万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926258
• 关键词: Antigens; Back; CXCL13 gene; Cancer Etiology; Cells; Cessation of life; Clinical Protocols; Clinical Research; Development; Disease; Genome; Human; Immune response; Immunotherapy; Laboratory Study; Lymphocyte; Malignant Neoplasms; Malignant neoplasm of lung; Methods; Mutate; Mutation; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Patients; Phenotype; Proteins; Reaction; Science; T-Cell Receptor; T-Lymphocyte; Therapeutic; Tumor-Infiltrating Lymphocytes; anti-PD1 antibodies; neoantigens; patient subsets; tumor

We have begun a clinical protocol to determine if resident lymphocytes in non-small cell lung cancer are reactive with tumor specific mutated "neo-antigens" and if so, whether they can be therapeutic if given patients using methods recently developed in the Surgery Branch (Tran et al, Science 2014). We are studying ways to sequence the genome of a patient's lung cancer, identify all mutated proteins, redisplay them effectively to the T-cells in their tumors and search for T-cells that can react to these mutated neo-antigens. In addition, we have developed a phenotypic signature in fresh tumor infiltrating lymphocytes that highly enriches for mutation reactivity to the point that new, previously unknown antigen reactivities can be discovered. This has identified CD39 and the expression of CXCL13 as driver markers for neoantigen reactive T-cells. This study also is attempting to find T-cell receptors that could be used to target commonly shared antigens in other patients (see Project #3).

我们已经开始制定临床方案，以确定非小细胞肺癌中的居民淋巴细胞是否与肿瘤特异性突变的“新抗原”反应性，如果是这样，如果使用最近在手术分支中开发的方法给予患者，是否可以治疗（Tran等，Science，Science 2014）。我们正在研究对患者肺癌的基因组进行测序，鉴定所有突变蛋白的基因组，有效地重新发挥其肿瘤中的T细胞，并寻找可以对这些突变的新抗原反应的T细胞。此外，我们在新鲜的肿瘤浸润淋巴细胞中开发了一种表型特征，高度丰富了突变反应性，以至于可以发现新的，未知的抗原反应性。这已经确定了CD39和CXCL13作为新抗原反应性T细胞的驱动器标记。这项研究还试图找到可用于靶向其他患者常见抗原的T细胞受体（请参阅项目＃3）。

项目成果

Proteogenomic Analysis Unveils the HLA Class I-Presented Immunopeptidome in Melanoma and EGFR-Mutant Lung Adenocarcinoma.

• DOI: 10.1016/j.mcpro.2021.100136
• 发表时间: 2021
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Qi YA;Maity TK;Cultraro CM;Misra V;Zhang X;Ade C;Gao S;Milewski D;Nguyen KD;Ebrahimabadi MH;Hanada KI;Khan J;Sahinalp C;Yang JC;Guha U
• 通讯作者: Guha U

A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers.

• DOI: 10.1016/j.ccell.2022.03.012
• 发表时间: 2022-05-09
• 期刊: CANCER CELL
• 影响因子: 50.3
• 作者: Hanada, Ken-ichi;Zhao, Chihao;Gil-Hoyos, Raul;Gartner, Jared J.;Chow-Parmer, Christopher;Lowery, Frank J.;Krishna, Sri;Prickett, Todd D.;Kivitz, Scott;Parkhurst, Maria R.;Wong, Nathan;Rae, Zachary;Kelly, Michael C.;Goff, Stephanie L.;Robbins, Paul F.;Rosenberg, Steven A.;Yang, James C.
• 通讯作者: Yang, James C.