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Tetracyclic compounds that promote the proliferation of double-negative T cells in vitro

A tetracyclic compound and cell body technology, applied in organic chemistry, drug combination, antineoplastic drugs, etc., can solve the problem of difficult to reach cell volume, and achieve the goal of promoting cell cycle and mitosis, promoting construction, and efficiently promoting DNT cell proliferation Effect

Active Publication Date: 2018-02-16
艾美斐生物医药科技(上海)有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, given that DN T cells only account for about 1-5% of peripheral blood mononuclear cells (PBMCs), it is difficult to achieve the amount of cells required for CAR-DN-T therapy

Method used

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  • Tetracyclic compounds that promote the proliferation of double-negative T cells in vitro
  • Tetracyclic compounds that promote the proliferation of double-negative T cells in vitro
  • Tetracyclic compounds that promote the proliferation of double-negative T cells in vitro

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0028] IMC-00239 can promote the expansion of CAR-DN-T without affecting the cell killing function of CAR-DN-T.

[0029] DN T cells sorted from peripheral blood mononuclear cells of healthy donors were infected with chimeric antigen receptor lentivirus, and treated with T cell receptor antibody and cytokine (Vehicle) and 0.5μM IMC-00239 combined with T Cell receptor antibody and cytokine stimulation, cultured for 14 days. The number of cells in the IMC-00239 group is about 7 times higher than that in the Vehicle group. Figure 6 shown. Comparing the IMC-00239 group with the cytokine group CAR-DN-T for cell killing ability, it was found that IMC-00239 had no significant effect on the cell killing ability of CAR-DN-T, refer to Figure 7 shown.

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Abstract

The invention discloses a tetracyclic compound capable of promoting in-vitro proliferation of double-negative T cells. The tetracyclic compound is IMC-00239, and the molecular formula of the tetracyclic compound is shown in the description. The invention relates to the tetracyclic compound which can be used for promoting in-vitro proliferation of the CD3<+> / CD4<-> / CD8<->double-negative T (DN T) cells and is selected from a compound library according to a high-throughput screening method, and provides a pharmaceutically acceptable salt and a prodrug of the tetracyclic compound. The compound is a restrainer of a Wnt signal channel, and can induce degradation of beta-Catenin of the DN T cells, shorten cell cycle and promote karyokinesis when being used in in-vitro experiments. The compound can effectively promote the construction of a CAR-DN-T in-vitro proliferation system, and help implementation of a CAR-DN-T cell factory.

Description

technical field [0001] The invention relates to a tetracyclic compound that promotes double-negative T cell proliferation in vitro in the field of biomedicine, in particular to a compound that promotes CD3 + / CD4 - / CD8 - Tetracyclic compounds for in vitro proliferation of double-negative T (DN T) cells. Background technique [0002] Immunotherapy is considered to be the third revolution in cancer treatment, in which chimeric antigen receptor T cell (CAR-T) technology targets CD19 + The excellent clinical trial results of acute B-lymphoblastic leukemia have attracted widespread attention in the medical field, and it is considered to be the most promising therapy to cure tumors. [0003] However, the current CAR-T therapy is to use the patient's own T cells to transform CAR-T cells, which has high requirements on the number, vitality and proliferation ability of the patient's T cells. In the practice of clinical trials, it was found that more than 80% of patients' T cells...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/52A61P35/00
CPCC07D209/52
Inventor 范国煌廖诗骅陈曦李润生
Owner 艾美斐生物医药科技(上海)有限公司
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