GPC-1 CAR-T Cells for Squamous Cell Carcinoma
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Solution Overview
Problem
Current CAR-T cell therapies are ineffective for treating solid tumors like squamous cell carcinoma due to lack of specific targeting and weak cytotoxic effects, with no reported success for genetically-modified T cells in treating solid tumors.
Innovation Solution
Development of chimeric antigen receptor (CAR) T cells specific to glypican-1 (GPC-1) using nucleic acid encoding an extracellular domain capable of binding to GPC-1, combined with intracellular signaling sequences, which are genetically modified and transferred into T cells to enhance specificity and cytotoxicity against GPC-1-expressing cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If antibody treatment is used for cancer cells, then specific targeting is achieved, but the cytotoxic effect is relatively weak and frequent administration is required
Solution Approach 1:
The patent combines the antibody variable region (for specific targeting) with T cell receptor signaling components (for cytotoxic effect) into a single chimeric antigen receptor. This merging allows the CAR-T cell to simultaneously achieve specific antibody-like targeting and potent T cell-mediated cytotoxicity, resolving the contradiction between weak cytotoxic effect and frequent administration requirements
Solution Approach 2:
The chimeric antigen receptor is constructed as a composite molecule integrating extracellular antibody variable regions (for antigen recognition) with intracellular signaling domains (for T cell activation). This composite structure enables both specific targeting and strong cytotoxic response in a single therapeutic agent
2Reliability
If CAR-T cells are used for lymphatic leukemia, then dramatic clinical effect is achieved, but no adequate effect is observed for solid tumors
Solution Approach 1:
The patent applies local quality by selecting a solid tumor-specific antigen (GPC-1) and designing a customized CAR with extracellular domains that specifically recognize this antigen. This localized adaptation of the CAR design to target solid tumor characteristics enables the therapy to be effective for solid tumors rather than just lymphatic leukemia
Solution Approach 2:
The invention changes the target antigen parameter from CD19 (lymphatic leukemia marker) to GPC-1 (solid tumor marker), and adjusts the CAR structure accordingly. This parameter change in antigen specificity and receptor design enables the CAR-T cells to effectively target and treat solid tumors
3Reliability
If conventional treatment methods (surgery, radiation, chemotherapy) are used, then cancer can be treated, but continuous monitoring is required due to metastatic nature
Solution Approach 1:
The CAR-T cells exhibit self-service characteristics by autonomously seeking out, recognizing, and destroying GPC-1-expressing cancer cells throughout the body. Once infused, these cells continuously patrol and eliminate metastatic cells without requiring external intervention or monitoring, providing long-term disease control
Data Source
AI summary
The purpose of the present invention is to produce a chimeric antigen receptor (CAR) specific to glypican-1 (GPC-1) and to treat squamous cell carcinoma with genetically modified cells capable of expressing the CAR. The present invention provides: a chimeric antigen receptor for use in the treatment and/or prevention of squamous cell carcinoma, said chimeric antigen receptor comprising an extracellular domain capable of binding toGPC-1, a transmembrane domain and one or multiple intracellular domains, wherein at least one of the intracellular domains is an intracellular domain containing a primary cytosolic signaling sequence or an intracellular domain containing both a primary cytosolic signaling sequence and a secondary cytosolic signaling sequence; a genetically modified cell capable of expressing the chimeric antigen receptor; and a cell preparation containing the cell.