Modified Immune Cells With PD-L1 Variants for Allogeneic CAR-T

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Allogeneic CAR-T therapies face challenges such as recognition and rejection by the host immune system, leading to reduced efficacy and immunosuppression, which compromises the treatment effectiveness of CAR-T cells.

Innovation Solution

Modified cells are engineered to be deficient in endogenous inhibitory checkpoint molecules and express variant ligands with reduced immunoinhibitory signaling capabilities, enhancing effector functions and reducing immunogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If allogeneic CAR-T cells are used to reduce manufacturing cost and variability, then production efficiency is improved, but the cells are recognized and rejected by the host immune system, reducing treatment efficacy

Engineering Contradiction:

Improveproduction efficiencyVSAvoidtreatment efficacy

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent extracts and removes the endogenous inhibitory checkpoint molecule from the allogeneic CAR-T cell, eliminating the source of immune recognition and rejection while maintaining the therapeutic function of the cell

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces a modified ligand as an intermediary that binds to the inhibitory checkpoint molecule to block its function, preventing immune rejection while preserving CAR-T cell efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

2Device complexity

If allogeneic CAR-T cells are used to provide off-the-shelf therapy, then manufacturing complexity is reduced, but immunosuppression occurs, reducing effector functions and cytotoxicity

Engineering Contradiction:

Improvemanufacturing complexityVSAvoideffector function

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The patent extracts the endogenous inhibitory checkpoint molecule from the CAR-T cell, removing the source of immunosuppression and preserving effector functions and cytotoxicity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent modifies the ligand expression levels or characteristics to optimize the balance between preventing immune rejection and maintaining effector function

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260027207A1Modified cells and uses thereof

Publication Date: 2026.01.29 BIORAY LABORATORIES INC

AI summary

Provided are modified immune cells, proteins encoding PD-L1 variants and polynucleotides encoding the same. Pharmaceutical compositions comprising the same and methods of treating diseases are also provided.