Immune Cell Nanoparticle Coating for Freeze-Thaw Viability
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Solution Overview
Problem
Immune cell therapies face challenges with the rapid decline in viability and function of immune cells during freezing-thawing treatments, limiting the effectiveness of immune cell-based therapies such as adoptive cell therapy for cancer treatment.
Innovation Solution
The use of nanoparticles comprising conservation agents like cytokine molecules (e.g., IL-15) covalently coupled with a degradable linker, which are associated with immune cells to enhance viability, proliferation, and cytotoxic activity after freeze-thaw cycles, forming a nucleated cell-nanoparticle complex.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If immune cells are frozen for storage, then cell viability and function are preserved during storage, but cell viability and function rapidly decline after thawing
Solution Approach 1:
The patent applies preliminary action by coating immune cells with protective agents (e.g., hydrogel, polymer, or lipid-based materials) before freezing. This pre-protection layer is formulated to specifically counteract freeze-thaw damage, maintaining cell membrane integrity and functionality throughout the storage and thawing process, thereby resolving the contradiction between long-term storage preservation and post-thaw viability
Solution Approach 2:
The patent implements beforehand cushioning by incorporating shock-absorbing protective coatings and cryoprotectants that cushion cells during freezing and thawing stress. These materials absorb mechanical and thermal shocks, preventing cell lysis and functional loss, thus enabling both extended storage duration and high post-thaw viability
2Adaptability or versatility
If freezing-thawing treatment is applied to immune cells, then storage and transport are enabled, but cell function and viability rapidly decline
Solution Approach 1:
The patent uses intermediary protective materials (hydrogels, polymers, lipids) that mediate between the harsh freezing-thawing conditions and the sensitive immune cells. These intermediaries form protective interfaces that shield cells from damage while allowing controlled thawing, thus enabling storage and transport capabilities without compromising cell function
Solution Approach 2:
The patent applies parameter changes by carefully controlling freezing rates, thawing temperatures, and protective agent concentrations to optimize cell survival. By adjusting these physical and chemical parameters, the method enables freezing-thawing processing that preserves both cell viability and therapeutic function
3Ease of manufacture
If existing protocols for isolation, storage, freezing, thawing, and expansion are used, then immune cell therapy procedures can be performed, but cell function is not adequately preserved
Solution Approach 1:
The patent merges multiple protective mechanisms into a unified protocol: combining physical protection (coatings), chemical protection (cryoprotectants), and controlled processing parameters. This integrated approach maintains ease of manufacture while significantly improving cell function conservation compared to conventional separate protocols
Data Source
AI summary
The present disclosure features, at least in part, methods for conserving cell function, e.g., immune cell function, e.g., after one or more cycles of freezing and/or thawing the nucleated cell. In embodiments, the methods comprise contacting an immune cell with a protein nanoparticle comprising an IL-15 complex.