Allergy Prevention By lgE Cytotoxic Peptide(ECP)Vaccine

LGE 细胞毒肽 (ECP) 疫苗预防过敏

基本信息

  • 批准号:
    6337195
  • 负责人:
  • 金额:
    $ 23.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-09-30 至 2003-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (Provided by the applicant): IgE-mediated allergic asthma, rhinitis, food allergy, atopic dermatitis, anaphylaxis cost annual 18 billions in medical costs and loss of productivity in this country. Regulation of IgE production by B cells is orchestrated by Th2 cytokines. This paradigm dictates a treatment modality of IgE-mediated hypersensitive diseases that diminishes endogenous levels of IL-4, thereby IgE production by IgE-committed B cells. Alternatively, studies initiated by PI indicated that following IgE immunization, CD8 T cells play an important role in inhibiting IgE production by IgE-committed B cells, and profound IgE deficiency ensued and is maintained in IgE-immunized mice. This observation leads to the current passive anti-IgE therapeutic product concept. However, this treatment modality suffers drawbacks in failing to inhibit IgE synthesis as well as to remove circulating IgE-anti-IgE complexes, which accumulates to levels 10 fold higher, compared to the levels prior to treatment. And it is yet to be determined whether patients may be given a second heavy dose without eliciting neutralizing antibodies, including internal image-type of antibodies that potentially can cause mast cell degranulation. It is imperative to design alternative therapeutic modality based on active IgE immunization with higher safety standards. Herein, we provide a long-term strategy of reducing IgE levels by active immunization with IgE cytotoxic peptides (ECP) that are independent of requirement of conformation. Since B cells and plasma cells of the IgE lineage exhibiting natural ECP onto the binding site pocket of MHC class I, these targets are Iysed by ECP-specific CTL due to active vaccination. The advantages of this commercial vaccine are: (i) ECP is sequence-dependent, and does not elicit anti-IgE; (ii) ECP is economic and its effect long-lasting. To achieve this immediate goal, our two Aims are: Aim I: To Determine the Structure of Natural Human IgE (huIgE) CTL Epitopes Restricted To HLA-A2.1 and Ascertain Their Efficacies with huIgE-Producing Cells. Aim II: To Determine Whether ECP-specific CTL Elicited By Active Immunization Inhibit Human IgE Production In A Pre-clinical Model of huIgE/HLA-A2.1 Transgenic Mice. PROPOSED COMMERCIAL APPLICATION: IgE cytotoxic peptide (ECP) vaccine aims at an open market of active allergy immunization. Unlike the conventional allergen-desensitization, ECP technology based on targeting the universal IgE epitope can desensitize allergic syndromes caused by a myriad of allergens with a booser dose. Furthernore, unlike the current passive anti-IgE therapy, ECP is economic for one or two injections; risk-free since it is directed to linear sequence not recognize by anti-IgE, as compared to the current anti-IgE therapy that may actually cause mast cell degranulation due to induction of anti-idiotype.
性状(由申请方提供):IgE介导的过敏性哮喘, 鼻炎、食物过敏、特应性皮炎、过敏反应每年花费180亿 医疗费用和生产力的损失。IgE的调节 B细胞的产生是由Th 2细胞因子协调的。这种模式决定了 IgE介导的过敏性疾病的治疗方式, IL-4的内源性水平,从而通过IgE定型B细胞产生IgE。 或者,PI发起的研究表明,在IgE 免疫后,CD 8 T细胞在抑制IgE产生中起重要作用 由IgE定型B细胞,和深刻的IgE缺乏症随之而来,并保持 在IgE免疫的小鼠中。这一观察结果导致目前的被动抗IgE 治疗产品概念。然而,这种治疗方式具有缺点, 在不能抑制IgE合成以及去除循环中的 IgE-抗IgE复合物,其累积水平比 治疗前的水平。目前还不确定患者是否 可以给予第二次大剂量而不引发中和抗体, 包括可能导致肥大的内部图像类型抗体 细胞脱颗粒设计替代治疗模式势在必行 基于更高安全标准的主动IgE免疫。在此我们 提供通过主动免疫降低IgE水平的长期策略, IgE细胞毒性肽(ECP)是独立的要求, 构象由于IgE谱系的B细胞和浆细胞表现出 将天然的ECP结合到MHC I类的结合位点口袋上,这些靶点是 由于主动接种,被ECP特异性CTL裂解。的优点 (i)ECP是序列依赖性的,并且不引起 抗IgE抗体;(ii)ECP经济有效,作用持久。实现这一 近期目标,我们的两个目标是:目标一:确定自然界的结构 HLA-A2.1限制性人IgE(huIgE)CTL表位及其确定 与huIgE产生细胞的功效。目标二:确定是否 主动免疫诱导的ECP特异性CTL抑制人IgE的产生 在huIgE/HLA-A2.1转基因小鼠的临床前模型中。 拟定商业应用: IgE细胞毒性肽(ECP)疫苗旨在打开主动过敏免疫市场。与传统的过敏原脱敏不同,基于靶向通用IgE表位的ECP技术可以以更大剂量脱敏由无数过敏原引起的过敏综合征。此外,与目前的被动抗IgE治疗不同,ECP对于一次或两次注射是经济的;无风险的,因为它针对的是不被抗IgE识别的线性序列,与目前的抗IgE治疗相比,目前的抗IgE治疗实际上可能由于诱导抗独特型而导致肥大细胞脱粒。

项目成果

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科研奖励数量(0)
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专利数量(0)

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Swey-Shen Chen其他文献

Swey-Shen Chen的其他文献

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{{ truncateString('Swey-Shen Chen', 18)}}的其他基金

Broadly neutralizing(BN) pan-IgE supersite vaccine for allergic asthma
用于过敏性哮喘的广泛中和 (BN) 泛 IgE 超级疫苗
  • 批准号:
    9341882
  • 财政年份:
    2017
  • 资助金额:
    $ 23.22万
  • 项目类别:
Targeting Galectin-3 with novel drugs for treatment of eczema
以 Galectin-3 为靶点治疗湿疹的新药
  • 批准号:
    7748108
  • 财政年份:
    2009
  • 资助金额:
    $ 23.22万
  • 项目类别:
Bi-functional Therapeutics for Allergy-BFTA
过敏双功能疗法-BFTA
  • 批准号:
    7668324
  • 财政年份:
    2009
  • 资助金额:
    $ 23.22万
  • 项目类别:
Allergy Protection by Active IgE B Cell Vaccines
活性 IgE B 细胞疫苗的过敏保护
  • 批准号:
    6693007
  • 财政年份:
    2003
  • 资助金额:
    $ 23.22万
  • 项目类别:
Allergy Protection by Active IgE B Cell Vaccines
活性 IgE B 细胞疫苗的过敏保护
  • 批准号:
    6585616
  • 财政年份:
    2003
  • 资助金额:
    $ 23.22万
  • 项目类别:
IMMUNIZATION WITH ANTIGENIZED VECTORS
使用抗原化载体进行免疫接种
  • 批准号:
    6543436
  • 财政年份:
    2001
  • 资助金额:
    $ 23.22万
  • 项目类别:
Allergy Prevention By lgE Cytotoxic Peptide(ECP)Vaccine
LGE 细胞毒肽 (ECP) 疫苗预防过敏
  • 批准号:
    6511373
  • 财政年份:
    2001
  • 资助金额:
    $ 23.22万
  • 项目类别:
REGULATION OF IGE ANTIBODY PRODUCTION IN VITRO
IGE 抗体体外生产的调控
  • 批准号:
    3445717
  • 财政年份:
    1985
  • 资助金额:
    $ 23.22万
  • 项目类别:
REGULATION OF IGE ANTIBODY PRODUCTION IN VITRO
IGE 抗体体外生产的调控
  • 批准号:
    3445718
  • 财政年份:
    1985
  • 资助金额:
    $ 23.22万
  • 项目类别:
REGULATION OF IGE ANTIBODY PRODUCTION IN VITRO
IGE 抗体体外生产的调控
  • 批准号:
    3445716
  • 财政年份:
    1985
  • 资助金额:
    $ 23.22万
  • 项目类别:

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被动或主动免疫可以改变圆环病毒 DNA 的感染过程吗?
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