Application of daunorubicin in preparation of antitumor drugs
Through the combination of daunorubicin and PD-1 inhibitor, CD8+ T cells are promoted, and the problem of unsatisfactory results of existing tumor treatment methods has been solved, and anti-tumor activity has been significantly improved, providing tumors such as colorectal cancer. New immunotherapy regimens improve patients' quality of life and long-term prognosis.
Patent Information
- Application Number
- CN202411454810.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-17
- Publication Date
- 2024-12-27
AI Technical Summary
The existing tumor treatment methods such as colorectal cancer are not effective, especially the anti-tumor activity of PD-1 inhibitors in immunotherapy has not been combined with daunorubicin, and the synergistic effect of the two has not been fully exerted.
Daunorubicin combined with PD-1 inhibitors can enhance the antitumor activity of PD-1 inhibitors by promoting CD8+ T cell activation, forming a new antitumor drug, including daunorubicin and PD-1. The combination of inhibitors is suitable for the treatment of tumors such as colon cancer, lung cancer, melanoma, and liver cancer.
The combination of daunorubicin PD-1 inhibitors significantly improves anti-tumor activity, enhances the activation function of CD8+ T cells, provides potential immunotherapy options, and improves the immune function and long-term prognosis of tumor patients.
Smart Images
Figure HDA0005090152950000011
Abstract
Description
Technical Field
[0001] The present application relates to the field of biomedicine, and more specifically, to an application of daunorubicin in the preparation of anti-tumor drugs. Background Art
[0002] Colorectal cancer (CRC) is a heterogeneous, chronic, multi-gene and inflammatory malignancy with different genetic and epigenetic changes, and its occurrence and development mechanisms are very complex. The main treatments for colorectal cancer are surgery and adjuvant chemotherapy, but the results are not ideal.
[0003] Immunotherapy has shown great advantages in tumor treatment, especially immune checkpoint inhibitor therapy based on promoting the tumor killing function of T cells. PD-1 (Programmed death-1) promotes T cell activation and enhances its anti-tumor activity by inhibiting T cell inflammatory response. Studies have shown that small molecule drugs promote T cell receptor (TCR) activation, which can significantly improve the anti-tumor function of T cells and enhance the anti-tumor activity of PD-1 inhibitors.
[0004] Daunorubicin hydrochloride (DNR) is a very important anti-tumor drug in anthracycline antibiotics. Previous studies have reported that DNR can target topoisomerase II (Topoisomerase II, Topo2) in tumor cells and inhibit DNA replication. However, whether DNR can promote the anti-tumor activity of PD-1 inhibitors has not been reported. Summary of the invention
[0005] The purpose of the invention of this application is to study whether daunorubicin can promote the anti-tumor activity of PD-1 inhibitors.
[0006] In order to achieve the above invention objectives, this application adopts the following technical solutions:
[0007] In a first aspect, the present application provides a use of daunorubicin in the preparation of an anti-tumor drug.
[0008] Furthermore, the tumor includes colon cancer, lung cancer, melanoma, and liver cancer.
[0009] In a second aspect, the present application provides the use of daunorubicin combined with a PD-1 inhibitor in the preparation of anti-tumor drugs.
[0010] Furthermore, daunorubicin enhanced the anti-tumor activity of PD-1 inhibitors through CD8+ T cells.
[0011] Furthermore, daunorubicin enhanced the anti-tumor activity of PD-1 inhibitors by promoting CD8+ T cell activation.
[0012] Furthermore, the tumor includes colon cancer, lung cancer, melanoma, and liver cancer.
[0013] In a third aspect, the present application provides an anti-tumor drug comprising daunorubicin as an active substance.
[0014] Furthermore, the anti-tumor drug includes daunorubicin and a PD-1 inhibitor used in combination as active substances.
[0015] Furthermore, the dosage form of the drug includes tablets, powders, granules, capsules, oral liquids, injections or sustained-release preparations.
[0016] In summary, this application has the following beneficial effects:
[0017] This application found that daunorubicin combined with PD-1 inhibitors can have better anti-tumor activity, and further found that daunorubicin enhances the anti-tumor activity of PD-1 inhibitors by promoting CD8+T cell activation. This application provides a potential immunotherapy solution for the clinical treatment of tumors, which is expected to improve the immune function and overall prognosis of tumor patients, and improve the quality of life and long-term prognosis of patients. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 :DNR enhances the anti-tumor activity of PD-1 inhibitors through CD8+ T cells; (AD) MC38 (A) cell line (1X10 6 / ), LLC (B) cell line (1X10 6 / ), Hepa1-6 (C) cell line (1X10 6 / ), B16F10(D) cell line (2X10 5 / mouse) (day 0), and DNR (1 mg / kg) and control vehicle were gavaged on day 7, and the tumor volume was measured and recorded every 2 days (A); on day 17, the mouse tumor tissue was obtained, digested into single cells, and flow cytometry was used to detect IFN-γ in mouse TILs in the MC38 model (A) + CD8 + (E) T cell ratio and Gzmb + CD8 + (F) T cell ratio, flow cytometry staining antibody CD8-FITC (1:500) was incubated at 4℃ for 15-20min, and the cells were washed once with PBS and then analyzed by eBioscience TMFixation / Perm Diluent was used to fix and punch cells overnight; cells were washed with 1xPermeabilization buffer and incubated with IFN-γ and Gzmb antibodies (1:200) at room temperature for 1 hour, and cells were reselected with PBS (200uL / well) and transferred to flow cytometry for detection. (AD) MC38 cells were inoculated as in A, and anti-PD-1 or isotype control Isotype (200μg / mouse; injected on days 7, 11, and 14, and once every 3 days thereafter) was injected intraperitoneally starting from day 7, and DNR (10mg / kg) and control were gavaged starting from day 7, and the tumor size of mice was recorded as in A. AF data represent three independent replicates, mean±SD. *P<0.05; ****P<0.0001; ns, nosignificance. DETAILED DESCRIPTION
[0019] The technical scheme and effects of the present application are further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the invention, rather than to limit the invention.
[0020] The following experimental materials and instruments were commercially available unless otherwise specified.
[0021] Example 1: DNR enhances the anti-tumor activity of PD-1 inhibitors via CD8+ T cells
[0022] (1) In vivo MC38 tumor model in mice and flow cytometry confirmed that DNR enhanced the anti-tumor activity of PD-1 inhibitors
[0023] First, C57BL / 6 mice were subcutaneously inoculated with MC38 cells (1×10 6 / mouse) to establish the MC38 tumor model in mice (day 0), and intraperitoneal injection of anti-PD-1 or isotype control Isotype (200 μg / mouse; injected on day 7, 11, 14, and once every 3 days thereafter), gavage control (PBS) and DNR (10 mg / kg), and the tumor size was recorded every 2 days (the results are shown in Figure 1 A). Flow cytometry detection of IFN-γ in TILs + CD8 + (E) T cell ratio and Gzmb + CD8 + (F) T cell ratio (results as shown in Figure 1 E, as shown in 1F).
[0024] (2) LLC tumor model in mice confirms that DNR enhances the anti-tumor activity of PD-1 inhibitors
[0025] First, LLC cells (1×10 6 / mouse) to establish LLC tumor model in mice (day 0), and intraperitoneal injection of anti-PD-1 or isotype control Isotype (200 μg / mouse; injected on day 7, 11, 14, and once every 3 days thereafter), gavage control (PBS) and DNR (10 mg / kg), and tumor size was recorded every 2 days (results as shown in Figure 1 B).
[0026] (3) The Hepa1-6 tumor model in mice confirmed that DNR enhanced the anti-tumor activity of PD-1 inhibitors
[0027] First, C57BL / 6 mice were subcutaneously inoculated with Hepa1-6 cells (1×10 6 / mouse) to establish a Hepa1-6 tumor model in mice (day 0). Starting from day 7, anti-PD-1 or isotype control Isotype (200 μg / mouse; injected on days 7, 11, and 14, and then injected every 3 days), and control (PBS) and DNR (10 mg / kg) were gavaged. The tumor size was recorded every 2 days (the results are shown in Figure 1 C).
[0028] (4) The B16F10 tumor-bearing model in mice confirmed that DNR enhanced the anti-tumor activity of PD-1 inhibitors
[0029] First, C57BL / 6 mice were subcutaneously inoculated with B16F10 cells (2×10 5 / mouse) to establish a B16F10 tumor model in mice (day 0). Starting from day 7, anti-PD-1 or isotype control Isotype (200 μg / mouse; injected on days 7, 11, and 14, and then injected every 3 days), and control (PBS) and DNR (10 mg / kg) were gavaged. The tumor size was recorded every 2 days (the results are shown in Figure 1 D).
[0030] The above results show that daunorubicin combined with PD-1 inhibitors can have better anti-tumor activity, and daunorubicin enhances the anti-tumor activity of PD-1 inhibitors by promoting CD8+T cell activation. This application provides a potential immunotherapy solution for the clinical treatment of tumors, which is expected to improve the immune function and overall prognosis of tumor patients, and improve the quality of life and long-term prognosis of patients.
[0031] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.
Claims
1. Application of daunorubicin in the preparation of anti-tumor drugs.
2. The use according to claim 1, characterized in that: The tumors include colon cancer, lung cancer, melanoma, and liver cancer.
3. Application of daunorubicin combined with PD-1 inhibitor in the preparation of anti-tumor drugs.
4. The use according to claim 3, characterized in that: Daunorubicin enhances the antitumor activity of PD-1 inhibitors via CD8+ T cells.
5. The use according to claim 4, characterized in that: Daunorubicin enhances the antitumor activity of PD-1 inhibitors by promoting CD8+ T cell activation.
6. The use according to any one of claims 2 to 5, characterized in that: The tumors include colon cancer, lung cancer, melanoma, and liver cancer.
7. An anti-tumor drug, characterized in that: Includes daunorubicin as the active ingredient.
8. The anti-tumor drug according to claim 8, characterized in that: It includes a combination of daunorubicin and a PD-1 inhibitor as active ingredients.
9. The anti-tumor drug according to claim 8 or 9, characterized in that: The dosage form of the drug includes tablets, powders, granules, capsules, oral liquids, injections or sustained-release preparations.