CD40L-Engineered Regulatory B Cell Expansion for Immune Therapy

Solution Overview

Problem

Current methods for expanding regulatory B cells (Bregs) are inefficient in producing sufficient numbers for immune therapy, particularly for conditions requiring large cell quantities, and are time-consuming.

Innovation Solution

A method involving isolation and engineering of B cells to express CD40 ligand (CD40L) using a retroviral vector, combined with activation and expansion in the presence of cytokines and inhibitors, to enhance Breg production and suppressive capacity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If current expansion protocols are used, then Bregs can be produced, but the quantity is insufficient for immune therapy

Engineering Contradiction:

Improvenumber of BregsVSAvoidexpansion efficiency

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

The patent applies preliminary action by pre-activating B cells with CD40L and CpG ODNs before expansion, and by engineering them to constitutively express CD40L. This preliminary activation and engineering step ensures that B cells are primed for rapid and robust expansion, directly addressing the insufficient quantity issue by preparing cells in advance with the necessary activation signals and molecular machinery for proliferation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by modifying the functional state of B cells through engineering them to express CD40L constitutively, and by culturing them with specific cytokines (IL-2, IL-4, IL-12) and inhibitors (anti-miR-155). These parameter changes in cellular phenotype and culture conditions dramatically enhance expansion efficiency and yield, transforming B cells from a non-expanding state to a highly proliferative state suitable for therapy.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If current expansion protocols are used, then Bregs can be produced, but the time required is excessive

Engineering Contradiction:

Improvenumber of BregsVSAvoidproduction time

Core Design Contradiction:

Quantity of substanceVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-activating B cells with CD40L and CpG ODNs before expansion, and by engineering them to constitutively express CD40L. This preliminary activation and engineering step ensures that B cells are primed for rapid and robust expansion, directly addressing the insufficient quantity issue by preparing cells in advance with the necessary activation signals and molecular machinery for proliferation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by modifying the functional state of B cells through engineering them to express CD40L constitutively, and by culturing them with specific cytokines (IL-2, IL-4, IL-12) and inhibitors (anti-miR-155). These parameter changes in cellular phenotype and culture conditions dramatically enhance expansion efficiency and yield, transforming B cells from a non-expanding state to a highly proliferative state suitable for therapy.

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If B cells are expanded using current methods, then some Bregs are produced, but suppressive capacity is insufficient

Engineering Contradiction:

Improvenumber of BregsVSAvoidsuppressive function

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent employs parameter changes by modifying the functional state of B cells through engineering them to express CD40L constitutively, and by culturing them with specific cytokines (IL-2, IL-4, IL-12) and inhibitors (anti-miR-155). These parameter changes in cellular phenotype and culture conditions dramatically enhance expansion efficiency and yield, transforming B cells from a non-expanding state to a highly proliferative state suitable for therapy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses anti-miR-155 as an intermediary molecule to enhance Breg suppressive function. By inhibiting miR-155, a molecule that normally suppresses Breg function, the patent indirectly enhances the suppressive capacity of expanded Bregs. This intermediary approach allows for functional enhancement without directly modifying B cell genetics, addressing the insufficient suppressive capacity issue.

Inventive Principle:

Principle #24Intermediary (Mediator)

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

The method produces highly suppressive Bregs in sufficient quantities for treating immune-related diseases, including autoimmune disorders and graft versus host disease, with enhanced suppressive capabilities against CD4+ T cell proliferation and cytokine production.

Implementation Method 1

engineering the B cells to express CD40 ligand (CD40L) using a retroviral vector

Methodology Applied

Scientific EffectRetroviral transduction:

Implementation Method 2

activating and expansion in the presence of cytokines and inhibitors, to enhance Breg production

Methodology Applied

Scientific EffectCytokine signaling:

Data Source

PatentUS12516100B2Methods for producing regulatory B cells and uses thereof

Publication Date: 2026.01.06 BOARD OF RGT THE UNIV OF TEXAS SYST

AI summary

Provided herein are methods for expanding populations of regulatory B cells comprising engineering a population of B cells to express CD40 ligand. Also provided herein are methods of treating immune disorders with the regulatory B cells.