Glycoengineering eCD4-Ig

糖工程 eCD4-Ig

基本信息

  • 批准号:
    10589151
  • 负责人:
  • 金额:
    $ 100万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-09 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

ABSTRACT We are developing eCD4-Ig, an antibody-like molecule constructed from CD4, a coreceptor-mimetic peptide, and an antibody Fc, as a long-acting injectable therapeutic for HIV. Our progress to-date includes having extended the plasma half-life of eCD4-Ig to the point that it now rivals or surpasses that of the leading broadly neutralizing antibodies (bNAbs) being developed as long-acting injectables. In a head-to-head comparison of pharmacokinetics (PK) in the human FcRn-transgenic mouse model, eCD4-Ig had significantly better PK than a VRC01 protein that had a half-life of 71 days in humans (Gaudinski et al., PLoS Med, 2018). With support from NIAID, we have developed a CHO cell line for manufacturing eCD4-Ig under cGMP conditions. However, in-depth analysis of the composition of the N-linked glycans (NLGs) at N297 of the Fc of the protein made by the cell line has highlighted a problem shared by the entire field: The large majority of the NLGs are forms detrimental to PK. This problem is particularly pronounced among the afucosylated forms that are active for antibody- dependent cell-mediated cytotoxicity (ADCC). Indeed, only a few percent of the NLGs are afucosylated forms that allow both ADCC and a long half-life. Therefore, we propose glycoengineering our cell line for manufacturing eCD4-Ig. To do so, we will develop a glycoengineering gene cassette, introduce it into the cell line, and derive a glycoengineered clone for manufacturing eCD4-Ig under cGMP conditions. Although our primary goal is to manufacture eCD4-Ig protein consisting almost entirely of a single long-lived glycoform that is active for ADCC, the same glycoengineering gene cassette can be used to manufacture other antibody therapeutics, including bNAbs, to similarly extend effector function and plasma half-life. This work will reduce the therapeutic concentration and increase the interval at which long-acting protein therapeutics for treating and preventing HIV infection can be dosed.
摘要

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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MICHAEL DAVID ALPERT其他文献

MICHAEL DAVID ALPERT的其他文献

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{{ truncateString('MICHAEL DAVID ALPERT', 18)}}的其他基金

SARS-CoV-2 vaccines based on RBDs with engineered glycosylation sites
基于带有工程化糖基化位点的 RBD 的 SARS-CoV-2 疫苗
  • 批准号:
    10867558
  • 财政年份:
    2023
  • 资助金额:
    $ 100万
  • 项目类别:
Process development for manufacturing eCD4-Ig
eCD4-Ig 制造工艺开发
  • 批准号:
    10603836
  • 财政年份:
    2023
  • 资助金额:
    $ 100万
  • 项目类别:
Glycoengineering eCD4-Ig
糖工程 eCD4-Ig
  • 批准号:
    10549884
  • 财政年份:
    2022
  • 资助金额:
    $ 100万
  • 项目类别:
Glycoengineering eCD4-Ig
糖工程 eCD4-Ig
  • 批准号:
    10326424
  • 财政年份:
    2021
  • 资助金额:
    $ 100万
  • 项目类别:
Engineering AAV capsids for enhanced transduction of skeletal muscle
改造 AAV 衣壳以增强骨骼肌转导
  • 批准号:
    10515802
  • 财政年份:
    2020
  • 资助金额:
    $ 100万
  • 项目类别:
Engineering AAV capsids for enhanced transduction of skeletal muscle
工程化 AAV 衣壳以增强骨骼肌的转导
  • 批准号:
    10080465
  • 财政年份:
    2020
  • 资助金额:
    $ 100万
  • 项目类别:
Project 3:Optimal use of ART in establishing functional cures
项目 3:ART 在建立功能性治疗中的优化应用
  • 批准号:
    10381479
  • 财政年份:
    2020
  • 资助金额:
    $ 100万
  • 项目类别:
Project 3:Optimal use of ART in establishing functional cures
项目 3:ART 在建立功能性治疗中的优化应用
  • 批准号:
    10625290
  • 财政年份:
    2020
  • 资助金额:
    $ 100万
  • 项目类别:
Engineering AAV capsids for enhanced transduction of skeletal muscle
工程化 AAV 衣壳以增强骨骼肌的转导
  • 批准号:
    10576418
  • 财政年份:
    2020
  • 资助金额:
    $ 100万
  • 项目类别:
Improving the pharmacokinetics, potency, and immunogenicity of eCD4-Ig
改善 eCD4-Ig 的药代动力学、效力和免疫原性
  • 批准号:
    10394340
  • 财政年份:
    2020
  • 资助金额:
    $ 100万
  • 项目类别:

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