Dual-Target CAR-T Cells for Immunosuppressive Solid Tumors

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Solution Overview

Problem

Solid tumors have an immunosuppressive microenvironment that inhibits the anti-tumor effects of CAR-T cells, primarily due to the presence of immunosuppressive cells such as regulatory T cells (Tregs) and immunosuppressive macrophages.

Innovation Solution

Modified CAR-T cells are designed to target both tumor cells and immunosuppressive cells by incorporating additional constructs that inhibit their function, with expression regulated by a T cell-activation-promoted promoter, enhancing the efficacy of CAR-T therapy for solid tumors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR-T cells are used to target tumor cells, then anti-tumor efficacy is improved, but the immunosuppressive microenvironment inhibits the therapeutic effect

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidimmunosuppressive microenvironment

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful immunosuppressive cells (Tregs and macrophages) into targets for CAR-T cell attack. By designing CAR-T cells with dual specificity - one arm targeting tumor cells and another targeting immunosuppressive cells - the therapy transforms the immunosuppressive microenvironment from a protective barrier into a source of additional therapeutic benefit, eliminating the very cells that were suppressing the anti-tumor response

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The CAR-T cells are engineered to perform multiple functions simultaneously: they maintain their primary tumor-targeting capability while acquiring an additional function to recognize and eliminate immunosuppressive cells. This multi-functionality is achieved through dual CAR constructs or bispecific CAR designs, allowing a single cell type to address both the tumor burden and the immunosuppressive microenvironment

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If additional constructs are added to target immunosuppressive cells, then therapeutic efficacy is enhanced, but device complexity increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidCAR-T cell construct complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges multiple functional elements into integrated CAR constructs. Rather than adding separate, independent components, the design combines tumor-targeting and immunosuppressive cell-targeting capabilities into unified CAR structures. This merging reduces the number of separate elements needed while achieving enhanced therapeutic efficacy through multi-specificity

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent employs nested structural organization where antigen-binding domains, signaling domains, and regulatory elements are hierarchically arranged within the CAR construct. The complex multi-specific CAR is built by nesting functional modules - such as placing antigen-binding domains within a chimeric receptor structure that itself is integrated into the T cell signaling apparatus - creating a compact yet highly functional architecture

Inventive Principle:

Principle #7Nested doll (Nesting)

Data Source

PatentUS12473343B2Targeted t cells with cytotoxicity toward immunosuppressive cells

Publication Date: 2025.11.18 THE GENERAL HOSPITAL CORP

AI summary

Described herein are methods for producing and utilizing T cells comprising a chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain specific for a target tumor antigen, and a polypeptide comprising an extracellular antigen binding domain specific for an extracellular polypeptide expressed on an immunosuppressive cell. The technology described herein is related to methods of treating cancer, specifically solid tumors, by targeting immunosuppressive cells found within the tumor microenvironment.