Hom-1 Macrophage Reprogramming Toward M1 Tumoricidal Activity
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Solution Overview
Problem
The limited understanding of how tumor-associated macrophage (TAM) plasticity is controlled by cell intrinsic factors restricts the effectiveness of targeting TAMs in cancer treatment, as they often promote tumorigenesis and suppress anti-tumor immunity.
Innovation Solution
Genetically modify macrophages or monocytes to express the Hom-1 polypeptide or increase the expression of M1 genes and inhibit M2 genes, converting them into M1-like macrophages with tumoricidal activities, and administer these modified cells to cancer patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tumor-associated macrophages (TAMs) are targeted for cancer treatment, then anti-tumor immunity may be enhanced, but the limited understanding of TAM plasticity control by cell intrinsic factors restricts treatment effectiveness
Solution Approach 1:
The patent uses Hom-1 as an intermediary molecule to control TAM plasticity. By introducing Hom-1 expression into macrophages, the patent mediates the transition from M2-like to M1-like phenotype, thereby enhancing anti-tumor immunity while overcoming the limited understanding of intrinsic control mechanisms
Solution Approach 2:
The patent changes the expression parameter of Hom-1 in macrophages to control their phenotypic plasticity. By upregulating Hom-1 expression, the patent shifts macrophages from M2-like (pro-tumorigenic) to M1-like (anti-tumorigenic) phenotype, thereby improving treatment effectiveness
2Object-generated harmful factors
If M2-like TAMs are present in advanced tumors, then tumorigenesis is promoted, but converting them to M1 phenotype requires overcoming limited understanding of plasticity control
Solution Approach 1:
The patent extracts the key control element (Hom-1) from the complex network of intrinsic factors that regulate TAM plasticity. By focusing on Hom-1 alone, the patent simplifies the control mechanism while effectively converting M2-like TAMs to M1 phenotype, thereby reducing tumorigenesis promotion
Solution Approach 2:
The patent changes the Hom-1 expression parameter to control the harmful effects of M2 TAMs. By upregulating Hom-1, the patent shifts the macrophage phenotype from M2-like (harmful) to M1-like (beneficial), thereby eliminating tumorigenesis promotion without requiring complex control of multiple factors
3Reliability
If genetically modified macrophages expressing Hom-1 are administered, then anti-tumor activity is enhanced, but the complexity of genetic modification increases
Solution Approach 1:
The patent uses Hom-1 as a mediator to achieve anti-tumor activity through a relatively simple genetic modification approach. By introducing only the Hom-1 transgene into macrophages, the patent achieves phenotypic conversion and enhanced anti-tumor activity without requiring complex multi-gene modifications
Data Source
AI summary
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.