WO-2026092367-A1 - METHOD FOR KILLING BRAIN TUMOR CELLS IN VITRO

Abstract

Disclosed is a method for killing brain tumor cells in vitro. According to the embodiments of the present invention, the method comprises: bringing isolated brain tumor cells into contact with ABBV-075 to kill brain tumor cells. According to the embodiments of the present invention, the method kills brain tumor cells in vitro more efficiently.

Inventors

• XI, Qiaoran
• ZHANG, LIWEI
• ZHOU, WEI
• XU, CHENG

Assignees

• 清华大学
• 首都医科大学附属北京天坛医院

Dates

Publication Date

20260507

Application Date

20251027

Priority Date

20241031

Claims (20)

1. A method for killing brain tumor cells in vitro, characterized by comprising: ABBV-075 was applied to isolated brain tumor cells to kill them.
2. A method for targeting brain tumor cells in vitro, characterized by comprising: ABBV-075 was contacted with a separated cell population, including brain tumor cells.
3. The method according to claim 1 or 2, characterized in that it comprises: The concentration of ABBV-075 is 1 nM to 1000 nM.
4. The method according to claim 1 or 2, characterized in that it comprises: The brain tumor occurs in at least one of the spinal cord, brainstem, pineal region, and thalamus.
5. The method according to claim 1 or 2, characterized in that it comprises: The brain tumor cells include H3.3K27M mutant diffuse endogenous pontine glioma cells.
6. The method according to claim 2, wherein the cell population further comprises normal brain cells.
7. The method according to claim 6, wherein the normal brain cells include at least one of glial cells and neuronal cells.
8. The method according to claim 1 is characterized in that it further comprises contacting the BRG1 inhibitor with the isolated brain tumor cells.
9. The method according to claim 8, wherein the BRG1 inhibitor comprises BRM014.
10. The use of the reagent in the preparation of the kit, the reagent including ABBV-075, the kit being used to inhibit the expression of CREB5 and/or ID1.
11. Use of reagents in the preparation of pharmaceuticals, said reagents including ABBV-075, said pharmaceuticals for the treatment and/or prevention of gliomas.
12. The use according to claim 11 is characterized in that the reagent further comprises a BRG1 inhibitor.
13. The use according to claim 12 is characterized in that the BRG1 inhibitor comprises BRM014.
14. The use according to claim 11 is characterized in that the glioma occurs in at least one of the spinal cord, brainstem, pineal region, and thalamus.
15. According to the use of claim 11, the glioma comprises H3.3K27M mutant diffuse endophytic pontine glioma.
16. A pharmaceutical composition for treating or preventing glioma, characterized in that it comprises: ABBV-075.
17. The pharmaceutical composition according to claim 16 is characterized in that it further comprises: a BRG1 inhibitor.
18. The pharmaceutical composition according to claim 17, wherein the BRG1 inhibitor comprises BRM014.
19. The pharmaceutical composition according to claim 16 or 17 is characterized in that the ABBV-075 and the BRG1 inhibitor are suitable for simultaneous or continuous administration.
20. The pharmaceutical composition according to claim 16 is characterized in that the glioma occurs in at least one of the spinal cord, brainstem, pineal region, and thalamus.

Description

Methods for killing brain tumor cells in vitro Technical Field This invention relates to the field of pharmaceuticals, and more specifically, to a method for killing brain tumor cells in vitro. Further, this invention relates to a method for targeting brain tumor cells in vitro, the use of reagents in the preparation of reagent kits, the use of reagents in the preparation of pharmaceuticals, a pharmaceutical composition, a method for inhibiting CREB5 expression, a method for treating brain tumors, and a method for promoting the differentiation of brain tumor cells into astrocytes. Background Technology Brain tumors are the most common malignant tumors of the central nervous system, characterized by high invasiveness, high recurrence rate, and treatment resistance. Diffuse intrinsic pontine glioma (DIPG) is a particularly challenging type of brain tumor occurring in the brainstem, typically affecting children and adolescents, and with an extremely poor prognosis. Classified, DIPG belongs to the H3K27M-mutant diffuse midline glioma (DMG-H3K27M). DMG is a newly added brain tumor category in the 2016 WHO classification of malignant tumors of the central nervous system (CNS). DMG occurs in the spinal cord, brainstem, pineal region, and thalamus; its clinical behavior is invasive. The H3.3K27M mutation is a common gene variant in DIPG and is closely associated with tumor invasiveness and treatment resistance. Despite some progress in in vitro killing of brain tumor cells in recent years, current methods for killing brain tumor cells still have many limitations. Current methods for killing brain tumor cells are often accompanied by serious side effects, and their killing effect is limited and their specificity in targeting brain tumor cells is poor. Therefore, there is an urgent need to develop a new method for killing brain tumor cells in vitro to improve the efficiency of killing brain tumor cells. Summary of the Invention The present invention aims to at least partially address one of the technical problems existing in the prior art. To this end, the present invention provides a method for in vitro killing of brain tumor cells. This invention is based on the following discoveries of the inventors: Current methods for killing brain tumor cells often have serious side effects, low killing efficiency, and poor specificity in targeting brain tumor cells. To overcome this problem, the inventors have proposed a method for killing brain tumor cells in vitro, which improves the efficiency of killing brain tumor cells in vitro and enhances the specificity of targeting brain tumor cells. In a first aspect, the present invention provides a method for in vitro killing of brain tumor cells. According to an embodiment of the invention, the method includes: contacting isolated brain tumor cells with ABBV-075 to kill the brain tumor cells. The method according to the embodiment of the invention can improve the efficiency of in vitro killing of brain tumor cells. In a second aspect, the present invention provides a method for targeting brain tumor cells in vitro. According to an embodiment of the invention, the method includes: contacting ABBV-075 with a separated cell population, said cell population including brain tumor cells. The method according to the embodiment of the invention can specifically target brain tumor cells in vitro. In a third aspect, the invention provides for the use of the reagent in the preparation of a kit. According to embodiments of the invention, the reagent comprises ABBV-075, and the kit is used to inhibit the expression of CREB5 and/or ID1. In a fourth aspect, the invention provides for the use of the reagent in the preparation of a medicament. According to an embodiment of the invention, the reagent comprises ABBV-075, and the medicament is used to treat gliomas. In a fifth aspect, the present invention provides a pharmaceutical composition for treating or preventing gliomas. According to an embodiment of the invention, the pharmaceutical composition comprises ABBV-075. The pharmaceutical composition according to embodiments of the invention is capable of improving the efficiency of in vitro glioma cell killing and improving the specificity of targeting glioma cells. In a sixth aspect, the present invention provides a method for inhibiting CREB5 expression. According to an embodiment of the invention, the method involves contacting ABBV-075 with isolated cells expressing CREB5 to inhibit the expression of said CREB5. The method according to an embodiment of the invention is capable of inhibiting CREB5 expression. In a seventh aspect, the present invention provides a method for promoting the differentiation of brain tumor cells into astrocytes. According to an embodiment of the invention, the method includes contacting isolated brain tumor cells with ABBV-075 to promote the differentiation of the brain tumor cells into normal glial cells. The method according to an embodiment of the invention is c