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Method of modifying macrophage differentiation and immunity

A macrophage and cell technology, applied in the field of changing macrophage differentiation and immunity, can solve the problems of the effectiveness and potential application of targeted TAMs, and the limited plasticity of TAMs.

Inactive Publication Date: 2018-09-04
朱正仑
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the effectiveness and potential application of targeting TAMs in cancer therapy is limited due to the limited understanding of how TAMs plasticity is controlled by cell-intrinsic factors.

Method used

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  • Method of modifying macrophage differentiation and immunity
  • Method of modifying macrophage differentiation and immunity
  • Method of modifying macrophage differentiation and immunity

Examples

Experimental program
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Embodiment

[0042] We determine the role of the human homeobox protein Hom-1 in the functional polarization of human macrophages. We found that Hom-1 promotes and is required for M1 activation of human macrophages, but not for the expression of key genes involved in M2 activation.

[0043] Using primary TAMs isolated from cancer, we found that Hom-1 expression was significantly reduced in TAMs compared with macrophages isolated from normal control tissues. We show that the expression profile of Hom-1 in TAMs correlates with TAM phenotypes. Furthermore, ectopic expression of Hom-1 converts TAMs into an M1-like phenotype. Both in vitro and in vivo data show that Hom-1 confers TAM tumoricidal activity. Taken together, our study demonstrates that Hom-1 converts TAMs into tumor-killing cells. We show that Hom-1-expressing TAMs (displaying an M1 phenotype) are strongly inhibitory to the growth of various cancers, suggesting a role for Hom-1-regulated TAMs as a novel mode of cancer therapy. ...

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Abstract

A method of treating a cancer, the method comprising: providing a genetically modified macrophage or monocyte that contains a nucleic acid sequence encoding a Hom-1 polypeptide or a fragment thereof that contains the Hom-1 homeobox domain, wherein the nucleic acid sequence is operably linked to a heterologous promoter and the modified macrophage or monocyte expresses the Hom-1 polypeptide or the fragment thereof; and administering the modified macrophage or monocyte to a subject with a cancer.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application No. 62 / 253,836, filed November 11, 2015, the contents of which are hereby incorporated by reference in their entirety. Background technique [0003] The role of immunity in tumorigenesis has been increasingly recognized. Macrophages are enforcers of innate and adaptive immunity and have been recognized as key components of tumors and their microenvironment. Numerous studies have demonstrated the role of tumor-associated macrophages (TAMs) in the growth, invasion and metastasis of almost all tumors. TAMs from circulating monocytes display a wide range of phenotypes, ranging from an M1-like phenotype in the early stages of selected tumors to an M2-like phenotype in most advanced tumors. Consistent with their role in promoting tumorigenesis, M2-like TAMs display a characteristic phenotype of elevated expression of IL-10, IL4, MMP, and VEGF, as well as decrease...

Claims

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Application Information

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IPC IPC(8): C12N5/0786C12N5/078C12N15/00
CPCC07K14/4703C12N5/0645A61P35/00A61K38/443C12Y101/01003A61K39/4622A61K39/4614A61K39/4644G01N33/5011C12Q1/6886C12Q2600/158C12Q2600/136C12Q2600/106G01N33/5055G01N33/5082G01N33/574G01N2333/4704C12N2510/00C12N2830/002A61K35/15A61P35/04A61P35/02A61K2121/00
Inventor 朱正崙
Owner 朱正仑
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