US-20260124302-A1 - CAR-T CELL WITH GOOD BLOOD-BRAIN BARRIER PERMEABILITY, PRODUCT, AND USE THEREOF

Abstract

Disclosed is a CAR-T cell with good blood-brain barrier permeability, a product, and use thereof, relating to the technical field of treatment of central nervous system diseases. Based on the study on CAR-T cell immunotherapy for central nervous system diseases, this disclosure provides a CAR-T cell with good blood-brain barrier permeability and a corresponding drug for treating or improving the central nervous system diseases. The CAR-T cell targets B-cell maturation antigens and highly expresses a chemokine receptor CXCR3 and chemokines CCL1, CCL3, and CCL4. This disclosure further provides a product for detecting and judging the blood-brain barrier permeability of the CAR-T cell, such as probes, reagents, and kits, which can accurately detect and judge the blood-brain barrier permeability of a specific CAR-T cell.

Inventors

• Daishi TIAN
• Chuan Qin
• Wei Wang
• Xiaowei PANG
• Luoqi ZHOU
• Minghao DONG
• Yang Yu
• Lulu XU
• Yuxin Liu

Assignees

• TONGJI HOSPITAL,TONGJI MEDICAL COLLEGE,HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY

Dates

Publication Date

20260507

Application Date

20251105

Priority Date

20240415

Claims (8)

1. 1 . A CAR-T cell with good blood-brain barrier permeability, wherein the CAR-T cell is used for treating or improving central nervous system diseases, and the CAR-T cell targets B-cell maturation antigens and highly expresses a chemokine receptor CXCR3 and chemokines CCL1, CCL3, and CCL4.
2. 2 . The CAR-T cell with good blood-brain barrier permeability according to claim 1 , wherein the CAR-T cell is derived from peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood.
3. 3 . A method for detecting the blood-brain barrier permeability of the CAR-T cell according to claim 1 that is not aimed at disease detection and diagnosis, wherein judgment is made by detecting expression levels of the chemokine receptor CXCR3 and the chemokines CCL1, CCL3, and CCL4 in cerebrospinal fluid, or by detecting and analyzing chemotaxis of the CAR-T cell based on single-cell transcriptome sequencing data.
4. 4 . A product for detecting the blood-brain barrier permeability of the CAR-T cell, wherein the CAR-T cell is the CAR-T cell as claimed in claim 1 , the CAR-T cell is used for treating or improving central nervous system diseases, and the product is used for detecting the expression levels of the chemokine receptor CXCR3 and the chemokines CCL1, CCL3, and CCL4 in cerebrospinal fluid.
5. 5 . The product according to claim 4 , wherein the product comprises a reagent or probe for detecting the expression levels of the chemokine receptor CXCR3 and the chemokines CCL1, CCL3, and CCL4.
6. 6 . The product according to claim 4 , wherein the product is a detection kit, a test strip, or a detection chip.
7. 7 . Use of the CAR-T cell according to claim 1 , used for preparing drugs for targeted treatment or improvement of central nervous system diseases.
8. 8 . The use according to claim 7 , wherein the central nervous system diseases are neuromyelitis optica spectrum disorders.

Description

TECHNICAL FIELD This disclosure relates to the technical field of treatment of central nervous system diseases, and in particular, to a CAR-T cell with good blood-brain barrier permeability and use in detecting the blood-brain barrier permeability of the CAR-T cell for treating the central nervous system diseases. SEQUENCE LISTING The sequence listing xml file submitted herewith, named “WI-US25-31222-P.xml”, created on Oct. 29, 2025, and having a file size of 6,144 bytes, is incorporated by reference herein. BACKGROUND Chimeric antigen receptor T-cell (CAR-T) immunotherapy is a type of immunotherapy. CAR-T cell immunotherapy is implemented by collecting and isolating T cells from a patient's blood, and then culturing and amplifying them in large quantities in vitro after genetically modifying them, and finally infusing them back into the patient's body to eliminate target cells in a targeted manner, thereby playing its unique therapeutic effect. At present, the CAR-T cell immunotherapy is mainly used for the clinical treatment of patients with hematological malignancies and malignant tumors, such as relapsed/refractory B-cell acute lymphoblastic leukemia, large B-cell non-Hodgkin lymphoma un-responded to conventional treatment, relapsed/refractory malignant lymphoma, and relapsed/refractory multiple myeloma, and shows remarkable curative effect and sustained persistence to these diseases. Due to its capability of directly inducing target cell death and self-amplification characteristics, the CAR-T cell immunotherapy has been recommended as the second-line treatment for B-cell lymphoma within one year after initial treatment. However, although the CAR-T cell immunotherapy has showed therapeutic effectiveness in many types of solid tumors and hematological tumors, due to its special structure of blood-brain barrier in the central nervous system (CNS), the CAR-T cell immunotherapy has not achieved satisfactory results in the treatment of CNS diseases. The blood-brain barrier is a dynamic barrier between the CNS and a blood circulation system, which strictly regulates the transport of substances between blood and brain/cerebrospinal fluid, provides a stable internal environment for the realization of a neurological function, protects the CNS from various harmful substances, and also becomes a barrier that drugs for treating CNS-related diseases have to face. Many drugs have been eliminated because they cannot cross the blood-brain barrier to reach an effective dose. In the treatment of CNS diseases, including central nervous system leukemia, brain tumors such as glioblastoma, encephalitis, and neuromyelitis optica spectrum disorders, there are high requirements for the capability of drugs to effectively cross the blood-brain barrier. In the process of the CAR-T cell immunotherapy of the central nervous system diseases, whether the CAR-T cell can effectively cross the blood-brain barrier to enter the central nervous system and play its targeted therapeutic effect is very important. Therefore, it is urgent to develop a reliable CAR-T cell with good blood-brain barrier permeability in the treatment of CNS diseases. SUMMARY This disclosure provides a CAR-T cell for treatment of central nervous system diseases and having good blood-brain barrier permeability, a product in detecting the blood-brain barrier permeability of the CAR-T cell, and corresponding use thereof. The objectives are achieved by the following technical solutions. Provided is a CAR-T cell with good blood-brain barrier permeability, where the CAR-T cell is used for treating or improving central nervous system diseases, and the CAR-T cell targets B-cell maturation antigens and highly expresses a chemokine receptor CXCR3 and chemokines CCL1, CCL3, and CCL4. This disclosure confirms that the CAR-T cell can effectively cross the blood-brain barrier. The CAR-T cell has good chemotaxis and a capability of activating chemotaxis-related pathways. Furthermore, the CAR-T cell is derived from peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood. This disclosure further provides a method for detecting the blood-brain barrier permeability of the aforementioned CAR-T cell that is not aimed at disease detection and diagnosis. Judgment is made by detecting expression levels of the chemokine receptor CXCR3 and the chemokines CCL1, CCL3, and CCL4 in cerebrospinal fluid, or by detecting and analyzing the chemotaxis of the CAR-T cell based on single-cell transcriptome sequencing data (for example, obtained by using the 10×genomics platform). A product for detecting the blood-brain barrier permeability of the aforementioned CAR-T cell is provided. The CAR-T cell is used for treating or improving central nervous system diseases, and the product is used for detecting the expression levels of the chemokine receptor CXCR3 and the chemokines CCL1, CCL3, and CCL4 in cerebrospinal fluid. Further, the product includes a reagent or probe for detecting the ex