Methods, compositions, and systems for activation and expansion of cells

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Solution Overview

Problem

Current immunotherapy technologies face challenges in developing platforms that allow for fine-tuning of surface and matrix rigidity while maintaining a high area-to-volume ratio, which is crucial for optimal T cell expansion and differentiation, especially for adoptive immunotherapy applications.

Innovation Solution

The development of electrospun mesh substrates comprising polydimethylsiloxane (PDMS) and polycaprolactone (PCL) with tunable fiber diameters and pore sizes, offering a biocompatible surface for cell expansion that mimics the in vivo environment, enhancing cell proliferation and differentiation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If rigid materials like polystyrene plastic and glass are used for T cell activation, then T cell expansion is achieved, but the substrate stiffness does not mimic in vivo conditions and may negatively impact cell activation, proliferation, and differentiation

Engineering Contradiction:

ImproveT cell expansion effectivenessVSAvoidsubstrate stiffness matching in vivo environment

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically varying the crosslinker ratio in PDMS substrates to achieve different stiffness values (Young's modulus ranging from 0.5 to 4 MPa). This allows optimization of substrate rigidity to better mimic in vivo conditions while maintaining effective T cell expansion, directly resolving the contradiction between expansion effectiveness and in vivo environmental matching.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by combining PDMS (polydimethylsiloxane) with varying crosslinker ratios to create substrates with tunable mechanical properties. This composite approach enables precise control over substrate stiffness while maintaining biocompatibility and expansion effectiveness, addressing both sides of the contradiction.

Inventive Principle:

Principle #40Composite materials

2Area of stationary object

If electrospun mesh substrates are used, then high surface area-to-volume ratio is achieved, but device complexity increases due to multiple parameters needing optimization

Engineering Contradiction:

Improvesurface area-to-volume ratioVSAvoidnumber of optimization parameters

Core Design Contradiction:

Area of stationary objectVSDevice complexity

Solution Approach 1:

The patent employs porous materials by using electrospun mesh substrates with controlled pore sizes (5-100 μm) and high surface area-to-volume ratios. The porous structure provides enhanced cell interaction surfaces while the systematic optimization approach manages the complexity of multiple parameters through methodical experimentation and characterization.

Inventive Principle:

Principle #31Porous materials

Data Source

PatentUS10301590B2Methods, compositions, and systems for activation and expansion of cells

Publication Date: 2019.05.28 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

The disclosure provides for compositions, systems, and methods of cell expansion, stimulation and/or differentiation. The disclosure further provides for a mesh substrate and associated methods capable of stimulating cell expansion, for example, T cell or stem cell expansion. In another aspect, the disclosure provides for an electrospun mesh substrate and methods of using thereof comprising a silicone rubber composition, for example, polydimethylsiloxane, PLC, or combinations thereof.