CXCR2 STAR T Cells for Solid Tumor Infiltration

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Solution Overview

Problem

Current T cell therapies, such as CAR-T therapy, have limited clinical applications and require improved efficacy, especially in targeting solid tumors, where the natural T cell receptor's signal transduction function can enhance T cell activation and specificity.

Innovation Solution

Development of a therapeutic T cell co-expressing CXCR2 and a Synthetic T cell Receptor and Antigen Receptor (STAR) against GPC3, comprising an antigen binding region and optimized constant regions, which enhances T cell targeting and killing ability of tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR-T therapy is used, then T cell therapy can be applied to treat cancer, but the therapeutic efficacy is limited and clinical applications are restricted

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidclinical application scope

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines CXCR2 receptor with STAR (Synthetic T cell Receptor and Antigen Receptor) to create a dual-receptor T cell therapy. This merging of two receptor systems allows the T cells to simultaneously achieve tumor targeting through STAR and enhanced activation/signaling through CXCR2, thereby improving therapeutic efficacy and expanding clinical applicability while maintaining specificity.

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If natural T cell receptor is used, then T cell activation and specificity are enhanced, but the receptor structure is complex and difficult to engineer

Engineering Contradiction:

ImproveT cell activation and specificityVSAvoidreceptor structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the T cell receptor system into two functional components: STAR for antigen recognition and specificity, and CXCR2 for signal transduction and activation. This segmentation allows each component to be independently optimized and engineered, reducing the overall complexity compared to using a complete natural TCR while maintaining enhanced activation and specificity functions.

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If T cell therapy is developed, then cancer treatment options increase, but the infiltration ability of T cells into tumors is insufficient

Engineering Contradiction:

Improvetreatment optionsVSAvoidT cell infiltration speed

Core Design Contradiction:

Adaptability or versatilityVSSpeed

Solution Approach 1:

CXCR2 acts as an intermediary receptor that mediates T cell interaction with the tumor microenvironment. By expressing CXCR2 on T cells, the therapy enhances chemokine signaling that facilitates rapid migration and infiltration of T cells into tumor tissues, thereby improving the speed of tumor penetration while expanding treatment options.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20240148787A1Co-expressed CXCR2 and t cells of star specific to GPC3, and use thereof

Publication Date: 2024.05.09 BRISTAR IMMUNOTECH LTD

AI summary

The invention relates to the field of biomedicine, in particular to a T cell co-expressing CXCR2 and a Synthetic T-Cell Receptor and Antigen Receptor (STAR) against GPC3, and uses thereof.