Allogeneic Hypoimmune CAR Biomimetic Nanovesicles for Reduced Cytokine Release
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Solution Overview
Problem
Current CAR whole cell therapies for cancer treatment face challenges such as cytokine release syndrome, B cell death, poor stability in the tumor microenvironment, hyperactivity leading to exhaustion, and off-target effects due to PD-1/PD-L1 signaling, limiting their efficacy against solid tumors.
Innovation Solution
Development of allogeneic, hypoimmunogenic biomimetic nanovesicles (BioNVs) equipped with membrane-embedded chimeric antigen receptors (CARs) and PD-1, PD-L1, or PD-L2 inhibiting agents to target cancer cells while mitigating immune system interference.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR whole cell therapy is used to target cancer cells, then cancer cell targeting capability is improved, but cytokine release syndrome and off-target immune responses occur
Solution Approach 1:
The patent segments the immune cell into a nanovesicle structure, separating the CAR targeting function from the harmful immune responses. The nanovesicle contains only the essential CAR component on its surface while excluding the intracellular machinery that produces cytokines and causes systemic immune reactions, thus maintaining cancer targeting capability while eliminating cytokine release syndrome
Solution Approach 2:
The patent extracts and removes the harmful elements (cytokine-producing machinery, activation markers) from the whole immune cell while retaining the beneficial CAR targeting function on the nanovesicle surface. This extraction process eliminates the source of cytokine release syndrome and off-target effects while preserving the cancer cell recognition capability
2Adaptability or versatility
If allogeneic cell lines are used to treat broader patient populations, then treatment accessibility is improved, but immune rejection and stability issues occur
Solution Approach 1:
The patent changes the physical and chemical parameters of the cell by transforming it into a nanovesicle structure with controlled size (50-500 nm), lipid composition, and surface properties. This parameter transformation creates a stable structure that resists degradation in the tumor microenvironment while maintaining the ability to target multiple patient populations through standardized CAR designs
3Productivity
If CAR whole cells are engineered with enhanced activity, then cancer cell killing efficiency is improved, but hyperactivity leading to exhaustion occurs
Solution Approach 1:
The patent extracts only the essential CAR targeting and signaling components needed for cancer cell killing while removing the intracellular machinery that leads to hyperactivity and exhaustion. The nanovesicle delivers a controlled, sustained killing effect without the metabolic burden that causes T cell exhaustion in whole cell therapies
4Reliability
If whole cell therapy is used to treat solid tumors, then tumor targeting is improved, but poor stability in hypoxic and acidic environment occurs
Solution Approach 1:
The patent changes the structural parameters of the therapeutic agent by creating a nanovesicle with a lipid bilayer membrane that is inherently more stable than whole cells. The nanovesicle structure resists degradation in hypoxic and acidic conditions, maintaining its integrity and CAR-mediated targeting capability throughout the challenging tumor microenvironment
Data Source
AI summary
Disclosed herein are compositions comprising allogeneic, hypoimmunogenic chimeric antigen receptor (CAR)-targetable biomimetic nanovesicles (BioNVs) and methods of using the same for the treatment, prevention, and/or amelioration of cancer.