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
- 来源:
- 关键词:
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.
描述(由申请人提供):IgE介导的过敏性哮喘,
鼻炎、食物过敏、特应性皮炎、过敏反应每年造成 180 亿美元的损失
这个国家的医疗费用和生产力损失。 IgE 的调节
B 细胞的产生是由 Th2 细胞因子协调的。这个范式规定
IgE 介导的过敏性疾病的一种治疗方式,可减少
IL-4 的内源水平,从而由 IgE 定向 B 细胞产生 IgE。
另外,PI 发起的研究表明,IgE 之后
免疫中,CD8 T细胞在抑制IgE产生中发挥重要作用
由 IgE 定向 B 细胞产生,随后发生并维持严重的 IgE 缺乏
在 IgE 免疫小鼠中。这一观察结果导致了目前的被动抗 IgE
治疗产品概念。然而,这种治疗方式也有缺点
未能抑制 IgE 合成以及消除循环
IgE-抗 IgE 复合物,其累积水平比
治疗前的水平。目前尚未确定患者是否
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抗体的内部图像类型
细胞脱颗粒。设计替代治疗方式势在必行
基于主动IgE免疫,安全标准更高。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) 独立于
构象。由于 IgE 谱系的 B 细胞和浆细胞表现出
天然 ECP 到 MHC I 类的结合位点口袋上,这些目标是
由于主动接种疫苗,被 ECP 特异性 CTL 裂解。这样做的优点
商业疫苗是: (i) ECP 是序列依赖性的,并且不会引起
抗IgE; (ii) ECP经济且效果持久。为了实现这一目标
近期目标,我们的两个目标是: 目标 I:确定天然物质的结构
人类 IgE (huIgE) CTL 表位限制于 HLA-A2.1 并确定其
产生 huIgE 的细胞的功效。目标二:确定是否
主动免疫引发的 ECP 特异性 CTL 抑制人类 IgE 产生
huIgE/HLA-A2.1 转基因小鼠的临床前模型。
拟议的商业应用:
IgE细胞毒性肽(ECP)疫苗旨在开放主动过敏免疫市场。与传统的过敏原脱敏不同,ECP技术基于针对通用IgE表位,可以通过加强剂量使多种过敏原引起的过敏综合征脱敏。此外,与目前的被动抗IgE疗法不同,ECP只需注射一两次即可经济;无风险,因为它针对的是抗IgE不识别的线性序列,而目前的抗IgE疗法实际上可能由于诱导抗独特型而导致肥大细胞脱颗粒。
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)
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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:
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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:
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:
Allergy Prevention By lgE Cytotoxic Peptide(ECP)Vaccine
LGE 细胞毒肽 (ECP) 疫苗预防过敏
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6511373 - 财政年份:2001
- 资助金额:
$ 23.22万 - 项目类别:
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