Dual-epitope car and dual-epitope car-t cell targeting CLL1, and use thereof

By designing a dual-epitope chimeric antigen receptor (CAR) targeting CLL1 and combining the co-stimulatory signal transduction domain and the chimeric switch receptor, the problems of bone marrow failure and immunosuppression of CAR-T cells in the treatment of AML are solved, and efficient killing and inhibition of CLL1-positive tumor cells are achieved, which has broad clinical application prospects.

WO2025190423A1PCT designated stage Publication Date: 2025-09-18CARBIOGENE THERAPEUTICS CO LTD
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Patent Information

Application Number
PCT/CN2025/091697
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-03-14
Filing Date
2025-04-28
Publication Date
2025-09-18

AI Technical Summary

Technical Problem

Existing CAR-T cell therapy in the treatment of AML has problems such as differences in the properties of myeloid antigens leading to bone marrow failure and a lack of alternative treatments. In addition, CAR-T cells that single-target tumor antigens have limited efficacy in AML and are difficult to effectively eradicate tumor cells.

Method used

A dual-epitope chimeric antigen receptor (CAR) was designed, which contains two single-domain antibodies and a transmembrane domain targeting CLL1, combined with a co-stimulatory signaling domain, and connected to the chimeric switch receptor PD-1 & CD27 through a self-cleaving peptide to form a dual-epitope CAR-T cell, which enhances the killing activity against CLL1-positive tumor cells and resists the immunosuppressive microenvironment.

Benefits of technology

Dual-epitope CAR-T cells significantly enhanced their ability to kill CLL1-positive tumor cells, secreted IFN-γ, inhibited tumor growth, and prolonged survival in mouse models. They had good in vivo tumoricidal activity and durability, and could effectively treat CLL1-positive cancers such as AML, MDS, and CML.

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Abstract

Provided are a dual-epitope CAR and dual-epitope CAR-T cell targeting CLL1, and the use thereof. The amino acid sequences of a chimeric antigen receptor and a fusion protein are SEQ ID NO: 1 and SEQ ID NO: 3, respectively. The dual-epitope CAR-T cell can secrete T cell-specific effector molecule IFN-γ and specifically kill CLL1+ target cells, and has tumoricidal activity in vivo. The present application can be used in the immunotherapy of CLL1 target-associated diseases.
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Citation Information

Patent Citations

  • Chimeric receptor combining immunosuppression receptor and tumor antigen receptor and application of chimeric receptor

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  • CLL1 and CD33 double-target chimeric antigen receptor and application thereof

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  • Double-target chimeric antigen receptor targeting CLL1 and NKG2D ligands and application thereof

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  • CLL1-targeting CAR-T cell as well as preparation method and application thereof

    CN116445415A

  • CLL1-CAR-T cell as well as preparation method and application thereof

    CN116515765A