HER2-Targeted Chimeric Antigen Receptors for Persistent T Cells

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Solution Overview

Problem

Existing tumor-specific T cell therapies face challenges with low anti-tumor specificity and durability due to the heterogeneous nature of solid tumors and potential off-target effects on non-cancerous cells, particularly in HER2-expressing cancers like breast and brain cancers.

Innovation Solution

Development of chimeric antigen receptors (CARs) with an extracellular HER2-targeting domain, transmembrane regions, and intracellular signaling domains, including costimulatory signals, engineered into T cells to enhance specificity and persistence, using vectors to transduce T cells like central memory T cells for adoptive cell therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If tumor-specific T cell therapies are used, then anti-tumor treatment is provided, but the T cells do not remain active in vivo for long enough periods

Engineering Contradiction:

Improveduration of T cell activityVSAvoidpersistence of T cells

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent segments the T cell therapy into multiple functional components: a CAR component for antigen recognition and targeting, and a cytokine component for survival and persistence signaling. This segmentation allows each component to be optimized independently - the CAR provides tumor-specific targeting while the cytokine component ensures long-term survival and activity of the engineered T cells in vivo.

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If T cells target self antigens, then broad anti-tumor coverage is achieved, but off-target effects on non-cancerous cells occur

Engineering Contradiction:

Improveanti-tumor coverageVSAvoidoff-target effects

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making the T cell therapy highly specific to particular tumor antigens through the CAR component. Rather than using broad self-antigen recognition that affects all cells expressing that antigen, the CAR is designed to recognize specific tumor-associated antigens with high affinity and specificity, concentrating the therapeutic effect locally on tumor cells while sparing non-cancerous cells.

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If solid tumors are targeted, then treatment of heterogeneous cancers is achieved, but tumor-specificity of T cells is reduced

Engineering Contradiction:

Improveapplicability to solid tumorsVSAvoidtumor-specificity

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent creates a universal platform for treating solid tumors through the cytokine-modified CAR T cells. The dual-component design (CAR plus cytokine) can be applied across different solid tumor types by changing the CAR antigen specificity while maintaining the same cytokine persistence mechanism. This multi-functional approach allows the same therapeutic strategy to work across heterogeneous solid tumors while preserving tumor-specificity through antigen-selective CAR design.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250333471A1Chimeric Antigen Receptors Targeting HER2

Publication Date: 2025.10.30 CITY OF HOPE

AI summary

Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain targeted to HER2, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.