STRATEGIES TO ENHANCE ADOPTIVE TRANSFER OF T CELL CLONES

增强 T 细胞克隆过继转移的策略

基本信息

  • 批准号:
    8172773
  • 负责人:
  • 金额:
    $ 15.51万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-05-01 至 2011-04-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The adoptive transfer of antigen-specific CD8+ effector T cells (TE) is being used to treat human viral and malignant disease with some success. However, the inconsistent or short in vivo persistence of transferred TE has been identified as a limitation of this approach. T cell growth factors such as interleukin (IL)-2 have been used to support the survival of transferred T cells. However, high-dose IL-2 can cause systemic toxicity, induces the expansion of CD4+FoxP3+ regulatory T cells (Treg), which can inhibit antitumor immunity, and may promote activationinduced cell death of transferred TE. IL-15 is a novel cytokine that has a critical role in the maintenance of T-cell memory and may be an alternative to IL-2 for supporting transferred T-cell survival. We administered IL-15 (2.515 ¿g/kg s.c.) to 8 macaques, either daily (n=3) or every 3 days (n= 5), and assessed toxicity and immunological effects. Daily IL-15 increased circulating NK and CD8+ T cells and expanded CD8+CD95+CCR7- effector memory (TEM) and CD95+CCR7+ central memory T cells (TCM). However, daily IL-15 (515 ¿g/kg) accumulated in vivo, causing reversible toxicities. Intermittent IL-15 treatment was safe, increased NK cells and CD8+ TEM or TCM, without boosting the CD4+ Treg. We are currently evaluating the administration of IL-15 to support adoptively transferred CD8+ TE in macaques. As previously reported, TCM-derived CD8+ TE transferred without cytokines persisted in vivo at low levels of 0.20.8% of CD8+ cells. By contrast, TE given with IL-15 persisted for up to 2 years at high levels (up to 10 % of CD8+ lymphocytes) after treatment in 2 animals. The transferred TE reverted to the memory pool and migrated to memory niches. Thus, IL-15 may provide an alternative to IL-2 to support the persistence of transferred TE in human immunotherapy.
这个子项目是众多研究子项目之一

项目成果

期刊论文数量(0)
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STANLEY R. RIDDELL其他文献

STANLEY R. RIDDELL的其他文献

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{{ truncateString('STANLEY R. RIDDELL', 18)}}的其他基金

Project 2: Targeting Neoantigens for Lung Cancer Immunotherapy
项目2:针对肺癌免疫治疗的新抗原
  • 批准号:
    10601293
  • 财政年份:
    2019
  • 资助金额:
    $ 15.51万
  • 项目类别:
Project 2: Targeting Neoantigens for Lung Cancer Immunotherapy
项目2:针对肺癌免疫治疗的新抗原
  • 批准号:
    10174871
  • 财政年份:
    2019
  • 资助金额:
    $ 15.51万
  • 项目类别:
Project 2: Targeting Neoantigens for Lung Cancer Immunotherapy
项目2:针对肺癌免疫治疗的新抗原
  • 批准号:
    10436174
  • 财政年份:
    2019
  • 资助金额:
    $ 15.51万
  • 项目类别:
Project 2: Targeting Neoantigens for Lung Cancer Immunotherapy
项目2:针对肺癌免疫治疗的新抗原
  • 批准号:
    10700908
  • 财政年份:
    2019
  • 资助金额:
    $ 15.51万
  • 项目类别:
Targeting Alloreactivity for Leukemia Eradication
针对白血病根除的同种异体反应性
  • 批准号:
    8277822
  • 财政年份:
    2011
  • 资助金额:
    $ 15.51万
  • 项目类别:
STRATEGIES TO ENHANCE ADOPTIVE TRANSFER OF T CELL CLONES
增强 T 细胞克隆过继转移的策略
  • 批准号:
    8357607
  • 财政年份:
    2011
  • 资助金额:
    $ 15.51万
  • 项目类别:
EVALUATING THE ENGINEERING OF CYTOMEGALOVIRUS-SPECIFIC CD8+ T CELL CLONES
评估巨细胞病毒特异性 CD8 T 细胞克隆的工程设计
  • 批准号:
    8172786
  • 财政年份:
    2010
  • 资助金额:
    $ 15.51万
  • 项目类别:
Targeted immunotherapy of breast cancer with central memory T cells
中央记忆T细胞对乳腺癌的靶向免疫治疗
  • 批准号:
    8181485
  • 财政年份:
    2010
  • 资助金额:
    $ 15.51万
  • 项目类别:
STRATEGIES TO ENHANCE ADOPTIVE TRANSFER OF T CELL CLONES
增强 T 细胞克隆过继转移的策略
  • 批准号:
    7958859
  • 财政年份:
    2009
  • 资助金额:
    $ 15.51万
  • 项目类别:
ANALYSIS OF A NOVEL SUBSET OF HUMAN CD8+ MEMORY CELLS WITH STEM CELL QUALITIES
具有干细胞特性的新型人类 CD8 记忆细胞亚群的分析
  • 批准号:
    7832350
  • 财政年份:
    2009
  • 资助金额:
    $ 15.51万
  • 项目类别:

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