"UNIQUE" TUMOR ANTIGENS RECOGNIZED BY CD8+ T CELLS

CD8 T 细胞识别的“独特”肿瘤抗原

基本信息

  • 批准号:
    6103361
  • 负责人:
  • 金额:
    $ 15.12万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1999
  • 资助国家:
    美国
  • 起止时间:
    1999-05-14 至 2000-04-30
  • 项目状态:
    已结题

项目摘要

The long-term objective is to understand the genetic origins and biological functions of unique, (i.e. individually distinct) antigens. These antigens lead to rejection of regressor tumors when transplanted into naive mice and of progressor tumors when transplanted into pre- immunized mice. Two types of unique antigens recognized by CD8+ T cells will be analyzed: those that must be lost by regressors before they can grow in a naive mice and those that can be retained by progressor variants. In the first Aim, it will be determined whether expression of a somatically mutated p68 peptide indeed gives rise to the rejection of the regressor tumor, by analyzing whether re-expression of the mutant gene by an antigen-loss variant reverts from a progressor to a regressor phenotype. If this is observed, it will further be determined whether re- expression of this antigen is sufficient even in established cancer to elicit tumor rejection. In Aim 2, it will be studies which changes in p68 helicase are observed in various cancers (in particular mutations and up- regulation of expression), and whether the already observed point mutation in the IQ domain of the gene results in oncogenic properties, while the wild-type p68 acts as a tumor suppressor gene. The main goal of Aim 3 is to confirm or refute the general principal that unique rejection antigens of UV-induced tumors are due to somatic mutations in a protein expressed at high levels in the cancer cells. The CD8+ T cell-defined unique 5117-RE tumor antigen which is consistently lost by progressor variants will be used as the model. If a mutant gene is identified, the potential significance of the mutations for the malignant process will be studied. The fourth Aim will be to identify the genetic origins of unique antigens that are retained on primary and variant progressor tumors and are insufficient to elicit tumor rejection by naive mice. It will be examined whether these antigens are also encoded by somatic tumor-specific mutations and whether these mutant peptides are equally or less immunogenic than mutant peptides expressed only by regressor tumors. Finally, we will determine whether loss of heterozygosity of the mutant genes encoding unique antigens on the progressor tumors is responsible for the extreme resistance of certain CTL epitopes to immunoselection, and we will analyze in standard assays the relevance of the mutant genes to the development of malignancy.
长期目标是了解遗传起源, 独特的(即单独不同的)抗原的生物学功能。 这些抗原在移植时导致消退肿瘤的排斥反应 移植到未处理的小鼠和进展肿瘤时, 免疫小鼠CD 8 + T细胞识别的两种独特抗原 将被分析:那些必须被回归变量丢失的数据, 生长在幼稚小鼠和那些可以保留的进展 变体。在第一个目标中,将确定是否表达一个 体细胞突变的p68肽确实引起了排斥反应, 回归肿瘤,通过分析是否重新表达突变基因, 抗原丢失变异体从进展因子恢复为消退因子 表型如果出现这种情况,将进一步确定是否重新 这种抗原的表达即使在已建立的癌症中也足够, 引起肿瘤排斥。在目标2中,将研究p68 在各种癌症中观察到解旋酶(特别是突变和上调, 表达调控),以及是否已经观察到的点突变 在基因的IQ域导致致癌特性,而 野生型p68作为肿瘤抑制基因。目标3的主要目标是 来证实或反驳独特的排斥抗原 的紫外线诱导的肿瘤是由于表达蛋白质的体细胞突变, 在癌细胞中处于高水平。CD 8 + T细胞定义的独特5117-RE 进展者变体持续丢失的肿瘤抗原将被 用作模型。如果发现了突变基因, 将研究突变对恶性过程的意义。 第四个目标是确定独特抗原的遗传来源 保留在原发性和变异进展肿瘤上, 不足以引起未处理小鼠的肿瘤排斥。它将被检查 这些抗原是否也由体细胞肿瘤特异性 突变以及这些突变肽是否等同或更少 与仅由退化肿瘤表达的突变肽相比,突变肽具有免疫原性。 最后,我们将确定是否杂合性丢失的突变体 编码进展肿瘤上独特抗原的基因负责 某些CTL表位对免疫选择的极端抗性,我们 将在标准测定中分析突变基因与 恶性肿瘤的发展。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Hans Schreiber其他文献

Hans Schreiber的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Hans Schreiber', 18)}}的其他基金

CD8+ T Cells and Immunological Tumor Regression
CD8 T 细胞和免疫肿瘤消退
  • 批准号:
    6609963
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
Three Laser BD Digital LSR
三激光BD数字LSR
  • 批准号:
    6580559
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
Administrative/Statistics/Imaging Core
行政/统计/成像核心
  • 批准号:
    8270394
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
Cancer Cells and Stroma: Eradication of Established Cancer by CD8+ T
癌细胞和基质:通过 CD8 T 根除已形成的癌症
  • 批准号:
    8375073
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
CD8+ T Cells and Immunological Tumor Regression
CD8 T 细胞和免疫肿瘤消退
  • 批准号:
    7229578
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
CD8+ T cells and Immunological Tumor Regression
CD8 T 细胞和免疫肿瘤消退
  • 批准号:
    7446448
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
CD8+ T Cells and Immunological Tumor Regression
CD8 T 细胞和免疫肿瘤消退
  • 批准号:
    6900349
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
CD8+ T cells and Immunological Tumor Regression
CD8 T 细胞和免疫肿瘤消退
  • 批准号:
    8270396
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
Cancer Cells and Stroma: Eradication of Established Cancer by CD8+ T
癌细胞和基质:通过 CD8 T 根除已形成的癌症
  • 批准号:
    8081108
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:
CD8+ T Cells and Immunological Tumor Regression
CD8 T 细胞和免疫肿瘤消退
  • 批准号:
    7118501
  • 财政年份:
    2003
  • 资助金额:
    $ 15.12万
  • 项目类别:

相似海外基金

A precision tumor neoantigen identification pipeline for cytotoxic T-lymphocyte-based cancer immunotherapies
用于基于细胞毒性 T 淋巴细胞的癌症免疫疗法的精准肿瘤新抗原识别流程
  • 批准号:
    10581488
  • 财政年份:
    2022
  • 资助金额:
    $ 15.12万
  • 项目类别:
A precision tumor neoantigen identification pipeline for cytotoxic T-lymphocyte-based cancer immunotherapies
用于基于细胞毒性 T 淋巴细胞的癌症免疫疗法的精准肿瘤新抗原识别流程
  • 批准号:
    10332251
  • 财政年份:
    2022
  • 资助金额:
    $ 15.12万
  • 项目类别:
Investigating the cell-based activity of a new class of cytotoxic T-lymphocyte antigen-4 (CTLA-4) small molecule inhibitors
研究一类新型细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 小分子抑制剂的细胞活性
  • 批准号:
    444149
  • 财政年份:
    2021
  • 资助金额:
    $ 15.12万
  • 项目类别:
    Operating Grants
Utilizing intranasal immunization to induce a cytotoxic T lymphocyte response and reduce metastatic burden in the lung
利用鼻内免疫诱导细胞毒性 T 淋巴细胞反应并减少肺转移负担
  • 批准号:
    10090666
  • 财政年份:
    2020
  • 资助金额:
    $ 15.12万
  • 项目类别:
Re-sensitization of immune checkpoint therapy resistant cancers to cytotoxic T-lymphocyte mediated killing
免疫检查点疗法耐药性癌症对细胞毒性 T 淋巴细胞介导的杀伤重新敏感
  • 批准号:
    412967
  • 财政年份:
    2019
  • 资助金额:
    $ 15.12万
  • 项目类别:
    Fellowship Programs
Mechanism for control of HIV-1 by cytotoxic T lymphocyte
细胞毒性T淋巴细胞控制HIV-1的机制
  • 批准号:
    17K10021
  • 财政年份:
    2017
  • 资助金额:
    $ 15.12万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding the regulation of cytotoxic T lymphocyte signalling and activity through single-cell genomics
通过单细胞基因组学了解细胞毒性 T 淋巴细胞信号传导和活性的调节
  • 批准号:
    MR/P014178/1
  • 财政年份:
    2017
  • 资助金额:
    $ 15.12万
  • 项目类别:
    Fellowship
Enhancing cytotoxic T lymphocyte (CTL) responses by directly loading CTL epitope vaccines onto MHC Class I complexes on the dendritic cell surface
通过将 CTL 表位疫苗直接负载到树突状细胞表面的 MHC I 类复合物上,增强细胞毒性 T 淋巴细胞 (CTL) 反应
  • 批准号:
    9299648
  • 财政年份:
    2017
  • 资助金额:
    $ 15.12万
  • 项目类别:
Discovery of Cytotoxic T Lymphocyte-inspired Bacteria Machine for Cancer Therapeutic Use Based on Synthetic Biological Approach
基于合成生物学方法发现细胞毒性 T 淋巴细胞启发的用于癌症治疗的细菌机器
  • 批准号:
    15K14415
  • 财政年份:
    2015
  • 资助金额:
    $ 15.12万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Elucidation of molecular mechanism of SV40 VP1 capsid protein to induce aimed cytotoxic T lymphocyte against viruses and its application for vaccine formulation.
阐明SV40 VP1衣壳蛋白诱导针对病毒的细胞毒性T淋巴细胞的分子机制及其在疫苗制剂中的应用。
  • 批准号:
    26860112
  • 财政年份:
    2014
  • 资助金额:
    $ 15.12万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了