Size-tunable synthetic particles with tunable optical properties and methods for using the same for immune cell activation

Inventors

Zhang, Daixuan • STONEBLOOM, Solomon • ARMAS, Juan • KETHAR, Harini • Thomas, Sunil • DE GEUS, Martina

Assignees

Slingshot Biosciences Inc

Abstract

A hydrogel particle, comprising a matrix comprising a polymerized monomer, said matrix comprising a plurality of micropores and a plurality of macropores, and one or more immunostimulatory biomolecules selected from the group consisting of an anti-CD3 antibody or antigen-binding fragment thereof, an anti-CD28 antibody or antigen-binding fragment thereof, and combinations thereof.

Core Innovation

The invention provides engineered particle systems that induce an immune cell response by contacting an immune cell with a particle comprising a matrix formed from a polymerized monomer. The matrix includes a plurality of micropores and a plurality of macropores, and the particle further includes one or more immunostimulatory or co-stimulatory biomolecules. The immune cell response includes activation and/or expansion, including conditions where the response is higher than an otherwise identical control particle lacking macropores.

The particle structure is refined through pore architecture, including constraints on macropore average diameter and relationships between macropore and micropore size. In related embodiments, the plurality of micropores are formed during monomer polymerization, and the particle diameter is between about 1 μm and about 25 μm.

The invention also addresses immune monitoring and cytometric device use through hydrogel particles that mimic target-cell optical or morphological properties. A method calibrates a cytometric device by inserting a hydrogel particle comprising a polymerized-monomer matrix with micropores and macropores and immunostimulatory or co-stimulatory biomolecules, measuring at least one optical or morphological property using the cytometric device, and calibrating based on the measurement.

Another method detects a target cell in a sample by inserting such a particle, measuring the particle optical or morphological property, then measuring the same properties of individual cells in the sample and determining whether the target cell is present based on the optical or morphological measurement similarity. The hydrogel particle has optical and/or morphological properties substantially similar to a target cell.

Claims Coverage

The independent claims in the provided set cover methods of inducing an immune cell response using porous micropore/macropore polymer-matrix particles with immunostimulatory or co-stimulatory biomolecules, and calibration and detection using hydrogel particles substantially similar to a target cell in optical or morphological property. Across the independent claims, the main inventive features are organized around porous polymer-matrix architecture, immune-stimulatory payload presentation, functional immune activation and/or expansion, and cytometric optical or morphological similarity-based calibration and detection.

Across the independent claims, the core coverage is methods that contact immune cells with micropore/macropore polymer-matrix particles carrying immunostimulatory or co-stimulatory biomolecules to induce activation and/or expansion, including macropore-specific structural constraints and higher response relative to particles lacking macropores. Additional independent coverage addresses cytometry by using hydrogel particles engineered to be substantially similar in optical or morphological property to a target cell for calibration and detection.

Stated Advantages

Documented Applications