Chimeric Antigen Receptor Compositions for Allogeneic Cell Therapy

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Solution Overview

Problem

Current CAR therapies face challenges in reducing graft versus host disease (GVHD) and immune rejection in allogeneic cell treatments, and there is a need for improved genetic compatibility and reduced immunogenicity in engineered cells.

Innovation Solution

Development of chimeric antigen receptors (CARs) with specific binder, hinge, transmembrane, costimulatory, and activation domains, combined with genetic modifications to reduce expression of MHC class I and II proteins and T cell receptors, enhancing compatibility and reducing immunogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If allogeneic engineered cells are used for CAR therapy, then therapeutic efficacy can be provided, but graft versus host disease (GVHD) and immune rejection occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidGVHD and immune rejection

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the genetic parameters of the engineered cells by reducing or eliminating the expression of HLA class I and II proteins and T cell receptors. This parameter change in protein expression levels reduces immunogenicity and GVHD while maintaining the CAR-mediated therapeutic efficacy against CD30-positive cells.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality modification by selectively reducing specific protein expressions (HLA class I, HLA class II, and T cell receptors) while preserving the CAR structure and function. This localized modification at the protein expression level allows the cells to maintain therapeutic capability while reducing harmful immune interactions.

Inventive Principle:

Principle #3Local quality

2Object-affected harmful factors

If HLA and T cell receptor expression is reduced, then immunogenicity and GVHD are reduced, but genetic compatibility challenges remain

Engineering Contradiction:

ImproveimmunogenicityVSAvoidgenetic compatibility

Core Design Contradiction:

Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent creates a universal approach by reducing multiple immunogenic markers (HLA class I, HLA class II, and T cell receptors) simultaneously in the engineered cells. This multi-target modification strategy provides broad reduction in immunogenicity across different donor-recipient mismatches, enhancing the versatility of allogeneic CAR therapy.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250268940A1Chimeric antigen receptor compositions and uses

Publication Date: 2025.08.28 INTELLIA THERAPEUTICS INC

AI summary

Compositions and methods for expressing a chimeric antigen receptor in a cell for use e.g., in adoptive cell transfer therapies.