Engineered Immune Cells With TCR Removal for Allogeneic Therapy

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing immune cell therapies face limitations in applicability and efficacy, particularly in terms of graft-versus-host disease, rejection, tumor inhibition, self-killing, inflammatory cascades, and heterogeneity of responses due to endogenous TCR expression in allogeneic cells.

Innovation Solution

Engineered immune cells are developed with nucleic acids encoding immune activating receptors and target-binding molecules linked to localizing domains, allowing for the downregulation of specific proteins and enhanced therapeutic efficacy by redirecting immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If allogeneic immune cells are used for therapy, then broader applicability is achieved, but graft-versus-host disease and rejection occur

Engineering Contradiction:

ImproveapplicabilityVSAvoidgraft-versus-host disease

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the endogenous TCR from allogeneic immune cells through genetic modification, eliminating the harmful graft-versus-host disease response while preserving the therapeutic function of the cells. This allows broader applicability of allogeneic cell therapy without the harmful effects of TCR-mediated rejection.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality modification by specifically targeting and modifying only the TCR-expressing components of the allogeneic cells while leaving other therapeutic functions intact. This selective modification reduces GvHD risk without compromising the overall therapeutic efficacy of the immune cells.

Inventive Principle:

Principle #3Local quality

2Reliability

If endogenous TCR expression is maintained in immune cells, then immune recognition function is preserved, but tumor inhibition and self-killing occur

Engineering Contradiction:

Improveimmune recognition functionVSAvoidself-killing

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent removes the harmful self-killing function mediated by endogenous TCR while extracting only the necessary immune recognition capabilities through engineered receptors. This eliminates fratricide and off-target toxicity while maintaining targeted tumor recognition and killing functions.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If immune cells are engineered with additional modifications, then therapeutic efficacy is enhanced, but device complexity increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidcell engineering complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by modifying the genetic composition of immune cells through targeted genetic engineering approaches. These parameter changes enhance therapeutic efficacy by eliminating harmful functions and improving persistence, while the modular nature of the genetic modifications keeps the engineering process manageable and scalable.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250354119A1Methods for enhancing efficacy of therapeutic immune cells

Publication Date: 2025.11.20 NATIONAL UNIVERSITY OF SINGAPORE

AI summary

The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.