Ex Vivo Immune Cell Generation via Apheresis Segmentation

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Solution Overview

Problem

Current methods for isolating and expanding T cells and NK cells from peripheral blood mononuclear cells (PBMCs) are inefficient for treating cancer and infectious diseases, necessitating improved techniques for obtaining these cells for therapeutic use.

Innovation Solution

A method involving therapeutic apheresis to purify CD3+ T cells and CD14+ monocytic cells, differentiating them into dendritic cells, and exposing these cells to antigenic peptides or adenoviruses to activate and expand T cells and NK cells, potentially incorporating epigenetic modulators like PRMT5, DNMT, and HDAC inhibitors to re-express tumor or infectious disease-specific peptides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods are used to isolate and expand T cells and NK cells from PBMCs, then the process is simpler, but the efficiency and therapeutic effectiveness are insufficient

Engineering Contradiction:

Improveefficiency of T cell and NK cell generationVSAvoidcomplexity of isolation and expansion process

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The apheresis product is segmented into distinct cell populations using flow cytometry-based purification. CD3+ T cells, CD14+ monocytes, and CD3-CD14- NK cells are separated into different fractions, allowing independent optimization of each cell type's expansion and function

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Dendritic cells are pre-differentiated from CD14+ monocytes and pre-loaded with tumor antigens or epigenetic modulators before being used to stimulate T cells. This preliminary preparation enhances the subsequent T cell activation and expansion efficiency

Inventive Principle:

Principle #10Preliminary action

Solution Approach 3:

Epigenetic modulators (PRMT5, DNMT, or HDAC inhibitors) are used as intermediary agents to re-express tumor peptides on dendritic cells, which then present these peptides to T cells, bridging the gap between dendritic cell antigen presentation and T cell activation

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If apheresis material is fully utilized for T cell purification, then T cell quality is improved, but NK cell availability decreases

Engineering Contradiction:

Improvequality of T cells for therapyVSAvoidavailability of NK cells

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The apheresis product is divided into multiple purified fractions: CD3+ T cells, CD14+ monocytes, and CD3-CD14- NK cells. This segmentation allows each cell type to be independently processed and optimized without depleting the others

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Flow cytometry parameters are optimized to distinguish and purify different cell populations based on their surface marker expression patterns (CD3, CD14), enabling simultaneous recovery of multiple cell types from the same starting material

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enables the generation of tumor-targeted lymphocytes and NK cells that can effectively treat cancer and infectious diseases by activating and expanding T cells and NK cells specifically recognizing and attacking tumor or infectious agents.

Implementation Method 1

the DC MHC-I or MHC-II present the peptide sequence or a portion thereof, thereby activating the DC

Methodology Applied

Scientific EffectMHC presentation:

Implementation Method 2

incorporating epigenetic modulators like PRMT5, DNMT, and HDAC inhibitors to re-express tumor or infectious disease-specific peptides

Methodology Applied

Scientific EffectEpigenetic modification:

Data Source

PatentUS20250011718A1Ex Vivo Generation of Immune Effector Cells from Apheresis Material Intermediates

Publication Date: 2025.01.09 IMMUNITYBIO INC

AI summary

Methods and compositions are provided herein for generating tumor targeted lymphocytes and/or tumor infiltrating lymphocytes and/or tumor targeted natural killer (NK) cells for use in the treatment of a cancer or an infectious disease. Also provided herein are methods of making and using the same.