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）是全世界女性的主要杀手。 NSCLC 患者需要额外的治疗选择。该提案旨在检查细胞毒性 T 淋巴细胞 (CTL) 对 NSCLC 的反应，以开发新的免疫治疗选择。该提案提出了一些问题，这些问题将定义和表征 NSCLC 特异性 CTL 识别的抗原。它还将研究一种将 NSCLC 抗原呈递给淋巴细胞前体的新方法。收集到的部分或全部信息可能会导致新型免疫治疗试剂在非小细胞肺癌中的临床试验。提出了四个具体研究目标。前两个具体目标将鉴定 HLA-A2 限制性 NSCLC 特异性 CTL，以及鉴定和表征被识别的抗原。在具体目标 3 中，我们将研究以 HLA-A3 开始的其他限制性元件在 NSCLC 肽呈递中的使用。 NSCLC特异性CTL的鉴定将涉及使用体外共培养方案（混合淋巴细胞肿瘤细胞培养，MLTC），结合从正常供者的外周血（PBMC）和HLA-A基因座匹配的同种异体长的NSCLC患者的外周血（PBMC）获得的淋巴细胞术语 NSCLC 肿瘤细胞系。 NSCLC 系经过基因修饰以表达淋巴细胞共刺激分子 CD80 (B7.1)。因此，携带I类MHC分子和潜在肿瘤抗原的肿瘤细胞将被制成有效的呈递细胞。具体目标 2 中 CTL 定义的抗原的鉴定将使用分子生物学技术和现有的基因克隆策略来完成。虽然我们提供的初步数据表明我们可以使用所描述的系统成功生成 HLA-A2 特异性 CTL，但特定目标 4 建议研究一种替代且可能更有效的 NSCLC 抗原呈递方法。提出了 NSCLC 肿瘤细胞系和树突状细胞之间的融合。所得体细胞杂交体将用于在体外产生特定的 CTL。这些在 NSCLC 中产生特异性 CTL 的尝试将极大地丰富我们对该疾病的免疫反应的知识库，并为疫苗或细胞免疫治疗方案提供关键试剂。

项目成果

Characterization of human non-small cell lung cancer (NSCLC) cell lines for expression of MHC, co-stimulatory molecules and tumor-associated antigens.

人类非小细胞肺癌 (NSCLC) 细胞系 MHC、共刺激分子和肿瘤相关抗原表达的表征。

• DOI: 10.1016/s0169-5002(01)00210-0
• 发表时间: 2001-08-01
• 期刊: Lung cancer
• 影响因子: 5.3
• 作者: J. M. Wroblewski;D. Bixby;C. Borowski;J. Yannelli
• 通讯作者: J. Yannelli

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

肿瘤细胞疫苗之路：细胞免疫疗法 20 年。

• DOI: 10.1016/j.vaccine.2003.12.036
• 发表时间: 2004-11-15
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: J. Yannelli;J. M. Wroblewski
• 通讯作者: 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。

• 发表时间: 2003-10
• 影响因子: 3.4
• 作者: Yannelli, John R;Hirscowitz, Edward;Wroblewski, Joanne M
• 通讯作者: Wroblewski, Joanne M

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。

• 发表时间: 2009-12
• 影响因子: 4.2
• 作者: Yannelli, John R;Tucker, Jo A;Hidalgo, Giovanna;Perkins, Sara;Kryscio, Richard;Hirschowitz, Edward A
• 通讯作者: Hirschowitz, Edward A

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。

• 发表时间: 2002-06-01
• 影响因子: 2.2
• 作者: Wroblewski, Joanne M;Copple, Angela;Batson, Lydia P;Landers, Cheri D;Yannelli, John R
• 通讯作者: Yannelli, John R