A Wholly Protein-based Self-assembly Nanoplatform for TNBC-specific Combination Therapy

用于 TNBC 特异性联合治疗的完全基于蛋白质的自组装纳米平台

基本信息

  • 批准号:
    10668398
  • 负责人:
  • 金额:
    $ 47.37万
  • 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:
    2022-08-01 至 2026-04-30
  • 项目状态:
    未结题

项目摘要

Abstract Triple-negative breast cancer (TNBC) is a unique type of breast cancer that does not express or overexpress estrogen receptor (ER), progesterone receptor (PR), and HER2. During the past several decades, the standard care of TNBC remains the highly toxic chemotherapy with little progress in more effective treatments. To address the urgent unmet need to develop targeted therapies specific for TNBC, we developed a totally protein-based nanoplatform called ProNano that is composed of two recombinant proteins, including the first an elastin-like polypeptide (ELP) nanocore that displays multiple calmodulin-binding short peptides on the surface, and the second a recombinant calmodulin protein genetically fused with a highly stable and modular protein domain possessing either tumor homing or therapeutic features. The docking of the ELP nanocore with a TNBC- targeting module together with a functional module with therapeutic feature results in bifunctional ProNanos that can be used for tumor-homing delivery of therapeutic agents for the combination therapy for TNBC. Three specific aims will be pursued in this project. The first specific aim is to develop a ProNano platform that allows tunable targeting of TNBC cells based on their surface antigen expression profiles. The second specific aim is to develop a bifunctional ProNano platform that allows tumor-specific blockade of the aberrant Wnt signaling for the treatment of TNBC. The third specific aim is to develop a bifunctional ProNano platform that allows tumor- specific inhibition of the ENPP1-catalyzed hydrolysis of extracellular cGAMP for combination immunotherapy of TNBC. The bifunctional ProNano platforms developed in this project have several major advantages over conventional nanoplatforms, including all protein components each can be precisely and genetically engineered, oriented and self-assembled introduction of both tumor homing and/or therapeutic moieties at desired ratios without need of any chemical conjugation, and use of highly stable and easily expressed modular polypeptides with no or low immunogenicity. Although we focus on the targeted treatment for TNBC, the ProNano platforms developed in this project can be easily adapted to address other cancer types simply by changing the tumor targeting module.
摘要

项目成果

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Rihe Liu其他文献

Rihe Liu的其他文献

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{{ truncateString('Rihe Liu', 18)}}的其他基金

Trimerization of the N-terminal Domain of ACE2 for Bifunctional Trapping of Future SARS-CoV-2 Variants
ACE2 N 末端结构域的三聚化,用于未来 SARS-CoV-2 变体的双功能捕获
  • 批准号:
    10288255
  • 财政年份:
    2021
  • 资助金额:
    $ 47.37万
  • 项目类别:
Trimerization of the N-terminal Domain of ACE2 for Bifunctional Trapping of Future SARS-CoV-2 Variants
ACE2 N 末端结构域的三聚化,用于未来 SARS-CoV-2 变体的双功能捕获
  • 批准号:
    10448485
  • 财政年份:
    2021
  • 资助金额:
    $ 47.37万
  • 项目类别:
Inhibition of GTPases and G proteins to treat human disease
抑制 GTP 酶和 G 蛋白来治疗人类疾病
  • 批准号:
    9352864
  • 财政年份:
    2016
  • 资助金额:
    $ 47.37万
  • 项目类别:
Inhibition of GTPases and G proteins to treat human disease
抑制 GTP 酶和 G 蛋白来治疗人类疾病
  • 批准号:
    9750731
  • 财政年份:
    2016
  • 资助金额:
    $ 47.37万
  • 项目类别:
Inhibition of GTPases and G proteins to treat human disease
抑制 GTP 酶和 G 蛋白来治疗人类疾病
  • 批准号:
    9159624
  • 财政年份:
    2016
  • 资助金额:
    $ 47.37万
  • 项目类别:
Targeting Ligand Core
靶向配体核心
  • 批准号:
    8540387
  • 财政年份:
    2013
  • 资助金额:
    $ 47.37万
  • 项目类别:
Novel Single Domain Antibodies with Multivalency and Multispecificity
具有多价性和多特异性的新型单域抗体
  • 批准号:
    8399006
  • 财政年份:
    2011
  • 资助金额:
    $ 47.37万
  • 项目类别:
Novel Single Domain Antibodies with Multivalency and Multispecificity
具有多价性和多特异性的新型单域抗体
  • 批准号:
    8588250
  • 财政年份:
    2011
  • 资助金额:
    $ 47.37万
  • 项目类别:
Novel Single Domain Antibodies with Multivalency and Multispecificity
具有多价性和多特异性的新型单域抗体
  • 批准号:
    8236055
  • 财政年份:
    2011
  • 资助金额:
    $ 47.37万
  • 项目类别:
Targeting Ligand Core
靶向配体核心
  • 批准号:
    7982958
  • 财政年份:
    2010
  • 资助金额:
    $ 47.37万
  • 项目类别:

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Lymph node-targeted codelivery of albumin-binding peptide antigens and di-adjuvant for melanoma combination immunotherapy
用于黑色素瘤联合免疫治疗的白蛋白结合肽抗原和双佐剂的淋巴结靶向共递送
  • 批准号:
    10522591
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Lymph Node-Targeted Codelivery of Albumin-Binding Peptide Antigens and Di-Adjuvant for Melanoma Combination Immunotherapy
用于黑色素瘤联合免疫治疗的白蛋白结合肽抗原和双佐剂的淋巴结靶向共递送
  • 批准号:
    10884052
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与犬HSP70结合的新型肿瘤抗原的鉴定及其在肿瘤免疫治疗中的应用
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    17K08108
  • 财政年份:
    2017
  • 资助金额:
    $ 47.37万
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    Grant-in-Aid for Scientific Research (C)
Allosteric Binding in Antibodies and Protein Antigens
抗体和蛋白质抗原的变构结合
  • 批准号:
    7684654
  • 财政年份:
    2008
  • 资助金额:
    $ 47.37万
  • 项目类别:
Allosteric Binding in Antibodies and Protein Antigens
抗体和蛋白质抗原的变构结合
  • 批准号:
    8131731
  • 财政年份:
    2008
  • 资助金额:
    $ 47.37万
  • 项目类别:
Allosteric Binding in Antibodies and Protein Antigens
抗体和蛋白质抗原的变构结合
  • 批准号:
    7499132
  • 财政年份:
    2008
  • 资助金额:
    $ 47.37万
  • 项目类别:
Allosteric Binding in Antibodies and Protein Antigens
抗体和蛋白质抗原的变构结合
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  • 财政年份:
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Innate Cellular Lectin-Mediated Binding of Xenogeneic Antigens
先天细胞凝集素介导的异种抗原结合
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先天细胞凝集素介导的异种抗原结合
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    6984696
  • 财政年份:
    2005
  • 资助金额:
    $ 47.37万
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Innate Cellular Lectin-Mediated Binding of Xenogeneic Antigens
先天细胞凝集素介导的异种抗原结合
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    7484257
  • 财政年份:
    2005
  • 资助金额:
    $ 47.37万
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