CDH17-Specific CAR-T Cells for Solid Tumor Targeting
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Solution Overview
Problem
Current cancer treatments, particularly for solid tumors like liver and stomach cancers, lack effective therapeutic targets and biomarkers, with CAR-T cell therapies showing limited efficacy and safety concerns due to expression in normal tissues, necessitating the development of cadherin-17 specific antibodies and cytotoxic cells for targeted cancer immunotherapy.
Innovation Solution
Development of cadherin-17 specific antibodies and cytotoxic cells, including monoclonal antibodies with high similarity to specific amino acid sequences, conjugated with cytotoxic moieties, and chimeric antigen receptors, designed to target cadherin-17 expressed on tumor cells while minimizing impact on normal tissues, to enhance cancer treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-T cell therapy is used to target tumor antigens, then anti-cancer response is enhanced, but safety concerns arise due to expression of target antigens in normal tissues
Solution Approach 1:
The patent applies local quality by engineering CAR-T cells with dual specificity - one arm targets the tumor antigen (GPC3 or CDH17) while the other arm targets normal tissue antigens (CD45 or CD326). This creates a localized functional difference where the cell can distinguish between tumor and normal tissues through differential antigen expression patterns, thereby enhancing anti-cancer efficacy while reducing toxicity to normal tissues.
2Ease of manufacture
If conventional cancer treatments are used, then treatment is available, but effective therapeutic targets and biomarkers are lacking for solid tumors
Solution Approach 1:
The patent uses cadherin-17 (CDH17) as an intermediary target - a protein normally expressed in intestinal epithelial cells but aberrantly overexpressed in various solid tumors including hepatocellular carcinoma and gastric cancer. By targeting this intermediary molecule that bridges normal tissue identity and tumor phenotype, the therapy achieves precise targeting of solid tumors while sparing most normal tissues, thereby improving both treatment availability and targeting precision.
3Reliability
If GPC3-targeted CAR-T cells are used, then HCC treatment is attempted, but expression of GPC3 in normal tissues causes adverse effects
Solution Approach 1:
The patent segments the targeting function by dividing the CAR structure into multiple independent antigen recognition domains. Instead of relying on a single antigen target (GPC3), the CAR-T cells are engineered to recognize multiple antigens simultaneously - GPC3 or CDH17 on tumor cells, combined with normal tissue markers like CD45 or CD326. This segmentation of targeting functions allows the system to achieve reliable HCC treatment while avoiding toxicity through the multi-specificity safety mechanism.
Data Source
AI summary
Embodiments of the present disclosure relate to cadherin-17 specific antibodies and cytotoxic cells for cancer treatment. For example, an antibody may have specificity for cadherin-17 and include an amino acid sequence having at least 70% similarity with an amino acid sequence selected from SEQ ID NO: 1-21.