Cell Therapy Delivery via Endothelial Disruption
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cell therapy approaches for treating tumors and inflammation face challenges in achieving effective enrichment of mesenchymal stem cells (MSCs) and T cells at target sites due to low migration efficiency across the endothelium, limiting their therapeutic efficacy.
Innovation Solution
Administration of vascular endothelial damaging agents, such as combretastatins or immunosuppressants, prior to or in combination with cell therapy to disrupt the endothelium, enhancing the enrichment and localization of therapeutic cells at tumor or inflammatory sites.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cell therapy is administered to treat tumors and inflammation, then therapeutic effect is achieved, but enrichment of therapeutic cells at target sites is insufficient due to low migration efficiency across endothelium
Solution Approach 1:
The patent applies preliminary action by administering endothelial damaging agents before cell therapy to pre-disrupt the endothelium at target sites. This preparatory step creates favorable conditions for subsequent therapeutic cell migration, allowing cells to more efficiently home to tumors and inflammatory sites by bypassing intact endothelial barriers that would otherwise impede their recruitment.
Solution Approach 2:
The patent converts the harmful effect of endothelial damage into a beneficial outcome. By intentionally damaging the endothelium with specific agents, the patent creates increased permeability and recruitment signals that enhance therapeutic cell enrichment at target sites. The harmful endothelial disruption is transformed into a useful mechanism for improving cell therapy delivery and efficacy.
2Productivity
If endothelial damaging agents are administered to enhance cell enrichment, then homing efficiency improves, but potential harm to healthy endothelium may occur
Solution Approach 1:
The patent applies local quality by using endothelial damaging agents that selectively target and damage endothelium at specific disease sites (tumors and inflammatory locations) rather than causing uniform damage throughout the body. This localized approach allows enhanced therapeutic cell homing to target sites while preserving healthy endothelium in non-affected tissues, thereby improving homing efficiency without excessive systemic harm.
Solution Approach 2:
The patent uses endothelial damaging agents as intermediaries that mediate between the therapeutic goal (enhanced cell homing) and the biological barrier (intact endothelium). These agents temporarily disrupt the endothelial barrier at target sites, facilitating therapeutic cell recruitment, and then the endothelium can recover. The intermediary agents enable controlled, transient damage that serves the therapeutic purpose while allowing for subsequent healing.
Data Source
Figure 1
Figure 2A
Figure 2B
AI summary
The invention relates to a cell therapy product comprising mammalian therapeutic cells, preferably mesenchymal stem cell (MSCs) or T cells, for use as a medicament in the treatment of a medical condition, preferably for the treatment of a tumor and/or malignant disease or a disease associated with inflammation, wherein said treatment comprises administration of an endothelial damaging agent to the subject prior to or in combination with the cell therapy product.