CD13-Targeted Chimeric Proteins for Tumor Immune Recruitment
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Solution Overview
Problem
Cancer cells develop strategies to evade immune detection and destruction, necessitating the need for novel therapeutic agents that can effectively target CD13, a Zn2+ dependent membrane-bound ectopeptidase highly expressed in tumor neovasculature and some tumor cells, to inhibit cancer growth and modulate endothelial cell functions.
Innovation Solution
Development of CD13-targeted chimeric proteins or chimeric protein complexes with targeting moieties that bind to CD13 and signaling agents like TNF or IFN, which can recruit immune cells to tumor sites, modulate endothelial cell functions, and enhance tumor antigen presentation, leading to tumor vasculature disruption and immune cell infiltration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer therapies are used, then tumor growth may be inhibited, but cancers develop strategies to evade immune detection and destruction
Solution Approach 1:
The patent combines targeting moieties (such as antibodies against CD13, CD3, or CD4) with signaling agents (such as TNF, IFN-γ, or their mutants) into chimeric proteins. This merging creates a single agent that can both target tumor-specific markers and deliver immune-stimulating signals, thereby overcoming immune evasion while maintaining therapeutic effectiveness.
Solution Approach 2:
The chimeric proteins act as intermediaries that bridge the gap between immune cells and tumor cells. The targeting moiety directs the chimeric protein to tumor cells or tumor-associated endothelial cells, while the signaling agent portion recruits and activates immune cells to the tumor site, facilitating immune-mediated tumor destruction.
2Reliability
If signaling agents like TNF are used to recruit immune cells, then immune cell infiltration increases, but systemic toxicity may occur
Solution Approach 1:
The chimeric proteins exhibit local quality by concentrating immune-stimulating activity specifically at the tumor site through the targeting moiety. The signaling agent (e.g., TNF or IFN-γ) is delivered locally to tumor cells or endothelial cells expressing specific markers, thereby recruiting immune cells to the tumor microenvironment while minimizing systemic exposure and associated toxicity.
Solution Approach 2:
The patent employs parameter changes by using mutant forms of signaling agents (e.g., TNF mutants with reduced cytotoxicity, IFN-γ mutants with altered activity profiles) that modulate the balance between immune cell recruitment and systemic toxicity. These parameter modifications allow for enhanced local immune activation while reducing harmful systemic effects.
3Measurement precision
If chimeric proteins with multiple components are developed, then targeting precision and immune activation improve, but molecular complexity increases
Solution Approach 1:
The patent merges multiple functional components (targeting moiety and signaling agent) into a single chimeric protein molecule. This consolidation achieves precise targeting (through the targeting moiety recognizing tumor-specific markers) and effective immune activation (through the signaling agent) while simplifying the overall therapeutic approach compared to using separate agents.
Solution Approach 2:
The chimeric proteins exhibit multi-functionality by combining targeting and immune-stimulating activities in a single molecule. Different targeting moieties (anti-CD13, anti-CD3, anti-CD4) can be paired with different signaling agents (TNF, IFN-γ, or their mutants) to create versatile chimeric proteins that can address various aspects of tumor immunology through a unified platform.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The CD13-targeted chimeric proteins or chimeric protein complexes effectively shrink or destroy tumor vasculature, activate tumor endothelium to recruit immune cells, and promote immune cell infiltration, resulting in tumor necrosis and reduced tumor growth with minimal side effects.
Implementation Method 1
a CD13-targeted chimeric protein or chimeric protein complex comprising a CD13 targeting moiety and a signaling moiety
Implementation Method 2
which can recruit immune cells to tumor sites, modulate endothelial cell functions, and enhance tumor antigen presentation
Data Source
AI summary
The present invention relates, in part, to chimeric protein or chimeric protein complex comprising a CD13 targeting moiety and a signaling agent (e.g., without limitation TNF or IFN-γ) and methods of treatment using such compositions.