CAR-T Extracellular Vesicles for Solid Tumor Targeting
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Solution Overview
Problem
Current CAR T-cell therapies for cancer, such as cytokine release syndrome and limited effectiveness against solid tumors due to challenges in overcoming the tumor microenvironment, necessitate the development of safer and more efficient anti-cancer treatments.
Innovation Solution
Isolation and use of extracellular vesicles (EVs) derived from activated T-cells expressing chimeric antigen receptors (CARs), specifically those with a particle diameter of 150 nm or more, which are cytotoxic and can target cancer cells effectively without the need for additional anti-cancer agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T-cell therapy is used to treat cancer, then anti-cancer effectiveness is improved, but severe side effects such as cytokine release syndrome and cytokine storm occur
Solution Approach 1:
The patent extracts and isolates extracellular vesicles (EVs) from activated CAR T-cells, separating the therapeutic anti-cancer components from the harmful elements. The EVs are purified to remove bulk T-cell components that cause cytokine release syndrome, while retaining the anti-tumor activity in the vesicular form
Solution Approach 2:
The patent creates a copy of the therapeutic function by transferring CAR expression to extracellular vesicles. The EVs carry copies of the CAR antigen receptors and can recognize and bind to tumor cells, replicating the target-specific killing capability of CAR T-cells without requiring live engineered T-cells
2Reliability
If CAR T-cell therapy is used to treat hematologic malignancies, then treatment effectiveness is improved, but ability to treat solid tumors is limited due to tumor microenvironment challenges
Solution Approach 1:
The patent enhances universality by formulating EVs that can function across multiple tumor types. The EVs carry CAR receptors that can be directed against various tumor-associated antigens, and the vesicular formulation itself can penetrate different tumor microenvironments including solid tumors, making the therapy versatile for both hematologic malignancies and solid tumors
Solution Approach 2:
The patent changes the physical and biological parameters of the therapy by using EVs instead of whole cells. The EVs have different size, surface properties, and metabolic requirements that enable them to overcome tumor microenvironment barriers, with size distribution and surface charge modified to enhance penetration and retention in solid tumor tissues
3Reliability
If extracellular vesicles with size greater than 150 nm are used, then apoptotic activity against cancer cells is improved, but complexity of EV isolation and characterization increases
Solution Approach 1:
The patent applies local quality by focusing on a specific size subset of EVs (those greater than 150 nm) that exhibit enhanced apoptotic activity. Rather than processing the entire EV population, the methodology targets and enriches for this functionally superior subpopulation, optimizing therapeutic effect while managing complexity through focused isolation strategies
Data Source
AI summary
The present invention provides extracellular vesicles (EVs) derived from T-cells expressing chimeric antigen receptors (CAR) specifically activated with an antigen to which the CAR bind specifically, pharmaceutical compositions comprising these vesicles as well as their use in treating cancer. In particular the present invention exemplifies EVs derived from activated T-cells expressing CAR that bind specifically to HER2 cancer antigen, pharmaceutical composition comprising these EVs and their use in treating a cancer overexpressing HER2, such as ovarian cancer and breast cancer.