CTL DEFINED ANTIGENS IN NON SMALL CELL LUNG CANCER

非小细胞肺癌中的 CTL 定义的抗原

• 批准号: 6376579
• 负责人: JOHN R. YANNELLI
• 金额: $ 27.14万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6376579
• 关键词: MHC class I antigen; antigen presenting cell; biopsy; cell population study; complementary DNA; cytotoxic T lymphocyte; dendritic cells; gene expression; genetic library; human tissue; hybrid cells; isoantigen; mixed tissue /cell culture; molecular cloning; neoplasm /cancer immunology; neoplastic cell; nonsmall cell lung cancer; nucleic acid sequence; transfection; tumor antigens

Non-small cell lung cancer (NSCLC), is a leading killer of both women and women around the world. Patients with NSCLC are in need of additional therapeutic options. This proposal seeks to examine the cytotoxic T lymphocyte (CTL) response against NSCLC in order to develop novel immunotherapeutic options. The proposal asks questions which will define and characterize the antigens recognized by NSCLC specific CTL. It also will investigate a novel means of presenting NSCLC antigens to lymphocyte precursors. Some or all of the information gleaned may lead to clinical trials of novel immunotherapeutic reagents in NSCLC. Four Specific aims are proposed for study. The first two Specific Aims will identify HLA- A2 restricted NSCLC specific CTL as well as identify and characterize the antigens being recognized. In Specific Aim 3, we will examine the use of other restriction elements beginning with HLA-A3, in the presentation of NSCLC peptides. The identification of NSCLC specific CTL will involve the use of an in vitro co- culture scheme (Mixed lymphocyte tumor cell culture, MLTC) combining lymphocytes obtained from peripheral blood (PBMC) of normal donors and NSCLC patients with HLA-A locus matched allogeneic long term NSCLC tumor cell lines. The NSCLC lines are gene modified to express the lymphocyte co-stimulatory molecule, CD80 (B7.1). Thus, the tumor cells bearing class I MHC molecules and potential tumor antigens will be made into efficient presenting cells. Identification of CTL defined antigens in Specific Aim 2 will be done using molecular biologic techniques and existing gene- cloning strategies. While we present preliminary data showing that we can successfully generate HLA-A2 specific CTL using the described system, Specific Aim 4 proposes to study an alternative and possibly more efficient means of NSCLC antigen presentation. Fusions are proposed between NSCLC tumor cell lines and dendritic cells. Resultant somatic cell hybrids will be used to generate specific CTL in vitro. These attempts to generate specific CTL in NSCLC will add greatly to our knowledge base of the immunological response to this disease as well as provide critical reagents for vaccine or cellular immunotherapy protocols.

非小细胞肺癌（NSCLC）是世界各地妇女和妇女的主要杀手。 NSCLC患者需要其他治疗选择。该建议旨在检查针对NSCLC的细胞毒性T淋巴细胞（CTL）反应，以开发新的免疫治疗选择。该提案提出的问题将定义和表征NSCLC特定CTL认可的抗原。它还将研究一种向淋巴细胞前体呈现NSCLC抗原的新方法。收集的一些信息可能会导致NSCLC中新型免疫治疗试剂的临床试验。提出了四个具体目标进行研究。前两个具体目标将识别HLA-A2限制了NSCLC特定的CTL，并识别和表征所识别的抗原。在特定目标3中，我们将研究以HLA-A3开头的其他限制元素的使用，在NSCLC肽的呈现中。 NSCLC特异性CTL的鉴定将涉及使用体外共同培养方案（混合淋巴细胞肿瘤细胞培养，MLTC），结合了从正常供体的外周血（PBMC）获得的淋巴细胞和HLA-A基因座匹配的HLA-A基因座的淋巴细胞与HLA-A基因座相匹配的长期nsclc Tumor nsclc Tumor cillc tumor cillc tamclc tamerclc tome。 NSCLC线经过基因修饰，以表达淋巴细胞共刺激分子CD80（B7.1）。因此，将带有I类MHC分子的肿瘤细胞和潜在的肿瘤抗原被制成有效的细胞。在特定目标2中鉴定CTL定义的抗原将使用分子生物学技术和现有的基因进行策略来完成。尽管我们介绍了初步数据，表明我们可以使用所述系统成功地生成HLA-A2特定的CTL，但特定的目标4提出了研究NSCLC抗原呈现的替代性和可能更有效的方法。提出了NSCLC肿瘤细胞系和树突状细胞之间的融合。所得的体细胞杂种将用于在体外产生特定的CTL。这些在NSCLC中产生特定CTL的尝试将大大增加我们对该疾病的免疫学反应的知识库，并为疫苗或细胞免疫疗法方案提供关键试剂。

项目成果

Cell surface phenotyping and cytokine production of Epstein-Barr Virus (EBV)-transformed lymphoblastoid cell lines (LCLs).

EB 病毒 (EBV) 转化的淋巴母细胞系 (LCL) 的细胞表面表型和细胞因子产生。

• DOI: 10.1016/s0022-1759(01)00565-8
• 发表时间: 2002
• 期刊: Journal of immunological methods
• 影响因子: 2.2
• 作者: Wroblewski,JoanneM;Copple,Angela;Batson,LydiaP;Landers,CheriD;Yannelli,JohnR
• 通讯作者: Yannelli,JohnR

On the road to a tumor cell vaccine: 20 years of cellular immunotherapy.

• DOI: 10.1016/j.vaccine.2003.12.036
• 发表时间: 2004-11
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: J. Yannelli;J. M. Wroblewski

Growth and functional reactivity of lymphocytes obtained from three anatomic compartments in patients with non-small-cell lung cancer (NSCLC).

从非小细胞肺癌 (NSCLC) 患者的三个解剖区室获得的淋巴细胞的生长和功能反应性。

• DOI: 10.1089/108497803770418283
• 发表时间: 2003
• 期刊: Cancer biotherapy & radiopharmaceuticals
• 影响因子: 3.4
• 作者: Yannelli,JohnR;Hirscowitz,Edward;Wroblewski,JoanneM
• 通讯作者: Wroblewski,JoanneM

Characteristics of PBMC obtained from leukapheresis products and tumor biopsies of patients with non-small cell lung cancer.

从非小细胞肺癌患者的白细胞去除术产品和肿瘤活检中获得的 PBMC 的特征。

• DOI: 10.3892/or_00000588
• 发表时间: 2009
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: Yannelli,JohnR;Tucker,JoA;Hidalgo,Giovanna;Perkins,Sara;Kryscio,Richard;Hirschowitz,EdwardA
• 通讯作者: Hirschowitz,EdwardA