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.
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
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)
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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
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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
- 批准号:
6511373 - 财政年份:2001
- 资助金额:
$ 23.22万 - 项目类别:
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