Hydrogel particles as feeder cells and as synthetic antigen presenting cells
Inventors
Nguyen, Anh Tuan • Kim, Jeffrey • Ahn, Keunho • Zhang, Daixuan
Assignees
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Publication Number
US-12312595-B2
Publication Date
2025-05-27
Expiration Date
Abstract
The present disclosure provides feeder hydrogel particles that can function to support the growth, proliferation, and/or activation of a target cell in culture. The present disclosure also provides methods of culturing target cells with feeder hydrogel particles.
Core Innovation
Synthetic feeder hydrogel particles and antigen-presenting-cell (APC) mimic hydrogel particles are described as supporting target cell growth, proliferation, and activation in culture. The hydrogel particle compositions include polymerizable monomers and can include bifunctional and biodegradable options to form a hydrogel matrix, which is configured to present bioactive signals to target cells while maintaining particle-based delivery in an aqueous mixture.
The hydrogel particle systems incorporate bioactive molecules such as cytokines, growth factors, extracellular matrix (ECM) components, and transcription factors. Controlled release occurs via degradation of the hydrogel matrix, including disulfide-cleavable matrices, and hydrogel properties are tuned through polymer composition, crosslinking, and surface functionalization while maintaining density.
The document describes APC signaling concepts using T-cell stimulatory and costimulatory molecules, including CD3/CD28 and interleukins such as IL-2, IL-15, and IL-21, as well as TNF superfamily signaling such as CD137 (4-1BB). Representative target cells include stem cells, T cells including CAR T cells, and NK cells, and magnetic hydrogel particle variants are described for immunomagnetic capture and subsequent recovery or clearance.
The document includes example performance metrics for magnetic capture and selection using hydrogel-based magnetic capture, including reported target cell purity and yield results that are described as comparable to Dynabeads in at least one example. The patent also discusses effects of hydrogel particles on flow cytometry scatter and downstream staining after cleavage or dissolution of the hydrogel, and kits are described as including feeder and/or APC hydrogel particles for use with target cells.
Claims Coverage
The partial content provides one independent claim (clm-00001). This independent claim covers separating a target cell from an aqueous mixture using a magnetic capture hydrogel particle that dissolves upon exposure to a reducing agent, thereby releasing the target cell after magnetic isolation. It includes three main inventive aspects: the disulfide-crosslinked magnetic hydrogel matrix, a target-binding ligand, and a two-stage process of magnetic isolation followed by reducing-agent dissolution to release the cell.
Disulfide-crosslinked magnetic hydrogel matrix for magnetic attraction and reducing-agent dissolution
A magnetic capture hydrogel particle comprises a hydrogel matrix with magnetic material embedded and/or encapsulated therein, the hydrogel matrix configured to be attracted to or repelled by a magnetic field, and disulfide crosslinks enabling the hydrogel matrix to dissolve upon addition of a reducing agent.
Target-cell-binding ligand on the dissolvable magnetic hydrogel particle
The magnetic capture hydrogel particle further comprises a ligand capable of binding the hydrogel matrix to the target cell.
Magnetic isolation followed by reducing-agent dissolving to release the target cell
The method incubates the aqueous mixture comprising the target cell with the magnetic capture hydrogel particle to produce a target cell-bound magnetic capture hydrogel particle, applies a magnetic field to isolate the target cell-bound particle, retrieves the isolated particle, and contacts the hydrogel matrix with a reducing agent to dissolve the matrix and release the target cell.
Across the single independent claim provided, the inventive concept centers on a magnetic capture hydrogel particle with disulfide crosslinks that dissolve upon reducing-agent addition, enabling magnetic isolation of a ligand-bound target cell followed by dissolution to release the target cell.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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