Preparation method and application of universal CAR-T cells targeting FLT3 gene editing

By screening the mouse monoclonal antibody platform to obtain anti-FLT3 antibodies, constructing chimeric antigen receptors and preparing allogeneic FLT3-CAR-T cells, the problem of the market lack of high-affinity antibodies and universal CAR-T cells with high anti-tumor activity was solved, achieving the effect of efficiently killing FLT3-positive tumor cells and reducing preparation costs.

CN120040594BActive Publication Date: 2025-09-23SICHUAN UNIV
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Patent Information

Application Number
CN202510195266.4
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-02-21
Publication Date
2025-09-23
Estimated Expiration
2045-02-21

AI Technical Summary

Technical Problem

The market lacks high-affinity antibodies targeting FLT3 and universal CAR-T cells with high anti-tumor activity. Traditional autologous CAR-T cell therapy has problems such as high preparation cost, small number of T cells, impaired function and long manufacturing cycle, causing patients to miss the best treatment opportunity.

Method used

By screening the mouse monoclonal antibody platform, we obtained anti-FLT3 antibodies or their antigen-binding fragments, constructed chimeric antigen receptors, prepared allogeneic FLT3-CAR-T cells, knocked out TCR and B2M using CRISPR-Cas9 technology, developed universal CAR-T cells, and carried out large-scale and industrialized manufacturing with standardized processes.

Benefits of technology

It achieves high-affinity binding to FLT3 antigen, significantly kills FLT3-positive tumor cells, reduces preparation costs, simplifies the manufacturing process, and ensures that patients can receive treatment in a timely manner.

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Abstract

The present invention discloses a preparation method and application of a universal CAR-T cell targeting FLT3 gene editing. The anti-FLT3 antibody or antigen-binding fragment thereof provided by the present invention includes CDRs in the heavy chain variable region, the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 6, 12 or 17, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO: 7. The chimeric antigen receptor is constructed using the FLT3-targeting antibody or antigen-binding fragment thereof as the antigen-binding domain, and the universal CAR-T cell prepared using T cells isolated from the peripheral blood of healthy donors has significant killing activity against FLT3-positive tumors such as acute myeloid leukemia, and can be used to prepare drugs for the prevention and treatment of FLT3-positive tumors.
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