[go: up one dir, main page]

CN120733048A - Pharmaceutical composition for treating lung squamous carcinoma and application thereof - Google Patents

Pharmaceutical composition for treating lung squamous carcinoma and application thereof

Info

Publication number
CN120733048A
CN120733048A CN202511223725.1A CN202511223725A CN120733048A CN 120733048 A CN120733048 A CN 120733048A CN 202511223725 A CN202511223725 A CN 202511223725A CN 120733048 A CN120733048 A CN 120733048A
Authority
CN
China
Prior art keywords
pharmaceutical composition
bortezomib
lung squamous
squamous carcinoma
lung cancer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202511223725.1A
Other languages
Chinese (zh)
Inventor
徐嵩
金鑫
祖玲玲
李彤
任凡
仲建国
葛坤坤
谢黄晟
甘景亮
彭思博
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tianjin Medical University General Hospital
Original Assignee
Tianjin Medical University General Hospital
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tianjin Medical University General Hospital filed Critical Tianjin Medical University General Hospital
Priority to CN202511223725.1A priority Critical patent/CN120733048A/en
Publication of CN120733048A publication Critical patent/CN120733048A/en
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05Dipeptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pulmonology (AREA)
  • Endocrinology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

本发明涉及一种用于治疗肺鳞癌的药物组合物及应用,属于医药技术领域。该药物组合物由蛋白酶体抑制剂与PD‑1通路抑制剂组成,其中蛋白酶体抑制剂优选为硼替佐米,PD‑1通路抑制剂优选为PD‑1单抗。具体给药剂量为硼替佐米0.75mg/kg/次,PD‑1抗体10mg/kg/次。该药物组合物特别适用于治疗肺鳞癌。本发明通过两种不同作用机制药物的联合使用,提高了对肺癌尤其是肺鳞癌的治疗效果,为肺鳞癌的临床治疗提供了新的治疗方案。

The present invention relates to a pharmaceutical composition and application for treating squamous cell lung cancer, and belongs to the field of medical technology. The pharmaceutical composition consists of a proteasome inhibitor and a PD-1 pathway inhibitor, wherein the proteasome inhibitor is preferably bortezomib, and the PD-1 pathway inhibitor is preferably PD-1 monoclonal antibody. The specific dosage is 0.75 mg/kg/time of bortezomib and 10 mg/kg/time of PD-1 antibody. The pharmaceutical composition is particularly suitable for treating squamous cell lung cancer. The present invention improves the therapeutic effect of lung cancer, especially squamous cell lung cancer, by the combined use of two drugs with different mechanisms of action, and provides a new treatment plan for the clinical treatment of squamous cell lung cancer.

Description

Pharmaceutical composition for treating lung squamous carcinoma and application thereof
Technical Field
The invention relates to the field of lung cancer treatment, in particular to a pharmaceutical composition for treating lung squamous cell carcinoma and application thereof.
Background
Lung cancer is the second cancer in global morbidity and mortality is the leading cancer, with non-small cell lung cancer (NSCLC) being the most common histological type of lung cancer, accounting for 30% of all lung cancer cases. Lung squamous carcinoma (luc), a major type of NSCLC, originates mainly from the bronchial epithelium. Because early symptoms of lung squamous carcinoma are not obvious, most patients are advanced in diagnosis, lose surgical opportunities, have limited systemic treatment options and have high disease-related mortality. Although targeted and immunotherapy has made significant progress in NSCLC treatment in recent years, the rate of detection of common driving mutations in squamous cell lung carcinoma is low, and targeted therapies directed against these pathways have been less effective in clinical trials.
Immunotherapy has become an important development in NSCLC therapy, and in particular PD-1/PD-L1 inhibitors have gained significant efficacy in the treatment of advanced NSCLC that is negative for driving gene mutations. However, most luc patients have advanced diagnosis, and even with the addition of PD- (L) 1 inhibitors, the median OS for luc patients with first line immune combination chemotherapy is only 17.1 months. In addition, existing targeted therapeutic drugs such as EGFR-TKI can obtain good response in the early stage when treating EGFR mutation positive NSCLC, but most patients can have acquired drug resistance phenomenon after 9-14 months, so that treatment failure and disease progression are caused.
At present, the lung squamous carcinoma has limited treatment options, lacks effective targeting treatment means, has limited back line treatment options, and is difficult to meet the personalized treatment requirements of different patients. In the prior art, the type and concentration of the proteasome inhibitor are not fully optimized, and the application value of the proteasome inhibitor in treating lung squamous carcinoma is difficult to fully develop, and particularly, the aspects of promoting immune response and enhancing T cell killing activity still need to be further explored and researched.
Some patents have been invented for solving the problem of poor lung squamous cancer treatment effect. For example, chinese patent No. 113750215A proposes a pharmaceutical composition for treating tumors, which aims to provide a treatment scheme for treating tumor patients by using immunotherapy aiming at activating tumor microenvironment and relieving immunosuppression. The invention utilizes the combination of carfilzomib and a PD-1 pathway inhibitor to treat a tumor patient, wherein the PD-1 pathway inhibitor is a PD-1 inhibitor or a PDL1 inhibitor. However, this patent still has the problem of requiring the development of more proteasome inhibitors and inhibitors of the PD-1 pathway to extend the range of cancer treatments.
Therefore, there is a need to develop new and effective treatments to address the therapeutic needs of squamous cell lung carcinoma. The proteasome inhibitor bortezomib was first introduced into the clinic as a proteasome inhibitor, and was first approved by the FDA for clinical treatment of multiple myeloma. The results provide a new thought for treating lung squamous carcinoma, but how to fully develop the application value of bortezomib in treating lung squamous carcinoma becomes a problem to be solved urgently.
Disclosure of Invention
In the prior art, the lack of effective targeted therapy of lung squamous carcinoma, poor combined chemotherapy effect of PD-1 monoclonal antibody and insufficient development of application value of a proteasome inhibitor in lung squamous carcinoma therapy exist. Accordingly, the present invention has been made to solve the above-mentioned problems, and provides a combination for treating squamous cell carcinoma of lung and its application.
The invention provides a pharmaceutical composition for treating lung squamous carcinoma, which aims to solve the technical problems of low lung squamous carcinoma driving mutation detection rate, poor targeting treatment effect, limited immune combined chemotherapy effect, easiness in generating drug resistance of the existing targeting drugs and the like, and has the technical effects of improving the lung squamous carcinoma treatment effect, prolonging the survival time of a patient and enhancing immune response.
The invention solves the technical problems by adopting the technical scheme that the invention provides a pharmaceutical composition for treating lung squamous carcinoma, which consists of a proteasome inhibitor and a PD-1 pathway inhibitor.
Preferably, the proteasome inhibitor is bortezomib.
Preferably, the PD-1 pathway inhibitor is PD-1 monoclonal antibody.
Preferably, the bortezomib dose is 0.75 mg/kg/time, and the PD-1 mab dose is 10 mg/kg/time.
The invention also comprises a medicine for treating lung squamous carcinoma, which comprises a) a medicine composition and b) a pharmaceutically acceptable carrier or auxiliary material.
The invention also comprises application of the pharmaceutical composition in preparing medicines for treating lung squamous carcinoma.
Description of advantageous effects
Compared with the prior art, the invention provides a pharmaceutical composition for treating lung squamous carcinoma and application thereof, and the pharmaceutical composition has the following beneficial effects:
1. The invention fully develops the application value of the proteasome inhibitor bortezomib in treating lung squamous carcinoma, and the single drug uses bortezomib to inhibit the growth of lung squamous carcinoma tumor, thereby remarkably improving the treatment effect of lung squamous carcinoma and overcoming the problem that the existing targeted therapeutic drug is easy to have drug resistance when treating EGFR mutation positive NSCLC;
2. according to the invention, the bortezomib and the PD-1 monoclonal antibody are combined to form a new treatment strategy, so that the treatment effect is remarkably improved;
3. According to the invention, through flow cytometry and immunohistochemical staining analysis, it is proved that bortezomib combined with PD-1 monoclonal antibody treatment can promote CD8+ T cell infiltration and enhance T cell killing activity, and more effective immunotherapy is realized;
4. The invention effectively solves the problems of low detection rate of lung squamous carcinoma driving mutation and poor targeted treatment effect by optimizing the use of bortezomib, particularly the combined use of the bortezomib and PD-1 monoclonal antibody, and provides a more comprehensive and effective treatment scheme for lung squamous carcinoma patients.
Drawings
FIG. 1 is a graph showing the effect of bortezomib in promoting killing of Peripheral Blood Mononuclear Cells (PBMC) against squamous carcinoma cells of the lung.
FIG. 2 is a graph showing the effect of bortezomib-treated lung squamous carcinoma cells in promoting release of a killer substance in T cells.
Figure 3 is a graph showing the effect of bortezomib alone in inhibiting the growth of lung squamous carcinoma.
Fig. 4 is a graph showing the effect of bortezomib in promoting the therapeutic effect of PD-1 mab in lung squamous carcinoma.
FIG. 5 is a graph of the effect of combination therapy in promoting infiltration and killing of T cells.
Detailed Description
In order to make the technical scheme of the present invention better understood by those skilled in the art, the technical scheme of the present invention will be further described in detail with reference to the accompanying drawings and the detailed description.
Example 1
Bortezomib promotes killing of Peripheral Blood Mononuclear Cells (PBMCs) against squamous carcinoma cells of the lung
1. The experimental method comprises the following steps:
(1) Bortezomib was purchased from selleckchem mg, and was dissolved in DMSO 2.5ml as a solvent to prepare a mother liquor at a concentration of 2 mg/ml.
(2) Isolation of human Peripheral Blood Mononuclear Cells (PBMC) by placing 5ml of fresh peripheral venous blood from healthy volunteers in EDTA-containing tubes, processing within 1 hour, centrifuging 1000g of blood, washing at room temperature for 5min, leaving the upper plasma layer, adding 3ml of PBS to the blood cells, adding 4ml of Ficoll to 15ml of tubes, slowly adding blood along the side wall to the tubes, centrifuging at room temperature for 800g, room temperature for 30min, removing the middle white membrane, adding PBS 2-3 times the volume, 1600 rpm, centrifuging at room temperature for 5min, adding 1ml of erythrocyte lysate after discarding the waste liquid, standing for 5min,1600 rpm, centrifuging at room temperature for 5min, discarding the supernatant, washing with 3ml of PBS, centrifuging at room temperature for 5min, discarding the supernatant, re-suspending with RPMI-1640 medium, and extracting 5ml of fresh peripheral blood to obtain about 5X 10 6 PBMC.
(3) Activation of PBMC the cell counting plate counts PBMC, resuspended in 2ml RPMI-1640 medium per 2X 10 6 PBMC, 10. Mu. L T CELL TRANSACT reagent was added and recombinant human interleukin IL-2 (20U/ml) was added and incubated for 3 days after homogenization.
(4) Co-culture with Lung squamous carcinoma cells two human Lung squamous carcinoma cells were used in this experiment, SK-MES-1, YTMC-90 were all from the university of Tianjin medical university Hospital lung cancer institute. SK-MES-1 cells were cultured in DMEM medium (Gibco) containing 10% fetal bovine serum, and YTMLC-90 cells were cultured in RPIMI1640 medium (Gibco) containing 10% serum. Lung squamous carcinoma cells in logarithmic growth phase are digested by pancreatin, counted after digestion is stopped, 1×10 5 cells are added to each well of a 24-well plate for plating, and pretreatment is carried out for 24 hours after the cells are attached, respectively with DMEM medium, 1640 medium as a control, or 20nM bortezomib. The original culture medium or medicine is removed, the culture medium or medicine is washed by PBS, then PBMC are added into a 24-well plate according to the ratio of tumor cells to PBMC of 1:5, the PBMC are harvested after co-culture for 24 hours, the 24-well plate is washed by PBS, and the tumor cells are fixed and stained by crystal violet.
2. As shown in figure 1, after the PBMC is added after the bortezomib pretreatment, the crystal violet staining shows that the surviving tumor cells are obviously reduced after the co-culture is finished. (darker staining of crystal violet represents more surviving tumor cells).
Example 2
1. Experimental methods SK-MES-1 treated with DMEM medium was used as control group in example 1, and bortezomib-pretreated SK-MES-1 was used as bortezomib group. PBMC from example 1 after co-cultivation with lung squamous carcinoma cells were blocked using a cell stimulating mixture (a mixture of phorbol 12-myristate 13-acetate (PMA), ionomycin, brefeldin A and monensin, available from ThermoFisher Co.) to stimulate PBMC cells for 4h, re-harvesting the cells, fc receptor binding inhibitors (available from Airbfish Co.) and CellBlox blocking buffer (available from ThermoFisher Co.). The fluorescently labeled CD45, CD3, CD4, CD8 antibodies (available from ThermoFisher corporation) were added to 80ul of flow-staining buffer (available from ThermoFisher corporation) at a volume of 5ul per sample, the final volume of staining was 100 ul per sample, the staining solution was added to the cell samples, and incubation was performed at 4 ℃ for 30 minutes in the dark. The cells were washed by adding flow cytometry staining solution. Centrifugation was performed at 400g for 5 minutes at room temperature. 100. Mu.L of IC fixative (phosphate buffer solution of paraformaldehyde in composition, pH 7.3, available from ThermoFisher) was added to fix the cells, followed by pulse vortex mixing. Incubate for 30 minutes at room temperature, protected from light. 1 Xof the membrane-disrupted solution was added thereto, and the mixture was centrifuged at 400g for 5 minutes at room temperature, and the supernatant was discarded. The cell pellet was resuspended in 100. Mu.L of 1 Xmembrane rupture fluid. The interferon-gamma, granzyme B antibodies with fluorescent markers were added to the sample at a volume of 5 ul/sample for detection and incubated at room temperature for 30 minutes. 1 Xof the membrane-disrupted solution was added, and the solution was centrifuged at 400g for 5 minutes at room temperature, and the supernatant was discarded, and the washing step was repeated 1 time. Stained cells were resuspended in 300ul of flow cytometry staining solution for detection.
2. As shown in figure 2, the flow type detection of the PBMC after co-culture shows that interferon-gamma in T cells co-cultured by lung squamous carcinoma cells treated by bortezomib has higher positive rate of granzyme B, which indicates that the killing activity of the T cells is stronger.
Example 3
1. Experimental methods the present experiment was performed using murine lung squamous carcinoma cell KLN205 (purchased from Meson cell Co.) in DMEM medium containing 10% fetal bovine serum, and after the cells had grown to logarithmic phase, they were digested with pancreatin, transferred to a 15ml centrifuge tube, centrifuged at 1000 rpm for 5min and the supernatant removed. The cell pellet was resuspended in 5ml PBS, spun at 1000 rpm for 5min, and the previous step was repeated again. Cell counting plates were used to count and prepare cell suspensions at a number of 5X 10 5 cells (50-100. Mu.l) per mouse. 10 mice (purchased from Vetong Liwa) were subcutaneously tumor-bearing, after alcohol sterilization in the inguinal region of the mice, tumor cell suspensions were injected subcutaneously using a syringe, and the needles were slowly withdrawn after injection. Tumors were grown to 50-100mm 3 in size and randomized into two groups of 5 tumors. Intraperitoneal injections of control solvent (DMSO after dilution) or bortezomib (0.75 mg/kg/time) were started and drug treatment was given on days 8 and 11. Tumor size [ V (mm 3)=0.5*L*W2 (L is tumor long diameter, W is tumor short diameter) ] was measured periodically, and the day 14 after the start of administration was taken as the endpoint (day 22 after tumor inoculation, as shown in the figure), mice were euthanized at the endpoint of the experiment, and tissues were harvested for subsequent detection.
2. As shown in the experimental result in figure 3, in the lung squamous cancer tumor-bearing mice, the tumor growth speed of the bortezomib group mice is obviously slower than that of the control group, and the tumor quality at the experimental end point is also smaller than that of the control group.
Example 4
1. The experimental method is that 20 DBA/2J mice are used for constructing lung squamous cancer tumor-bearing models, the construction method is the same as that of the example 3, and the lung squamous cancer tumor-bearing models are randomly divided into 4 groups according to the tumor size after the tumor formation, wherein the 4 groups are respectively a control group, a PD-1 monoclonal antibody group, a bortezomib group and a bortezomib+PD-1 monoclonal antibody group (combined group). Bortezomib (0.75 mg/kg/time) or control solvent (DMSO after dilution) was given for intraperitoneal injection on days 9 and 12. PD-1 mab (10 mg/kg/dose) or IgG treatment (IgG as a control for PD-1 mab, administered in control and bortezomib groups) was given on days 10, 13, 16 and 19. Tumor size [ V (mm 3) =0.5×lw2 (L is tumor long diameter, W is tumor short diameter) ]wasmeasured periodically, the final day of PD-1 mab treatment was taken as the endpoint (day 23 after tumor inoculation), mice were euthanized at the endpoint of the experiment, and tissues were harvested for subsequent detection.
2. As shown in the experimental results in figure 4, in four groups of tumor-bearing mice, the tumor growth rate of the bortezomib combined PD-1 monoclonal antibody group is slowest, has obvious differences with a control group and also has obvious differences with a PD-1 monoclonal antibody treatment group, and shows that the combined treatment effect is superior to that of the PD-1 monoclonal antibody treatment.
Example 5
1. The experimental method comprises the following steps:
1. Production of paraffin sections
(1) The tumor tissues harvested in example 4 were fixed with 4% formaldehyde solution. The samples were washed 3 times for 5 minutes in phosphate buffer.
(2) The treatment was performed with 70%, 80% and 90% ethanol solution for 30 minutes, respectively, followed by 95% and 100% ethanol solution (twice each for 20 minutes), followed by 1:1 100% ethanol and xylene mixture for 15 minutes, followed by xylene alone to be transparent.
(3) Pouring the melted paraffin into a prepared container, rapidly transferring the paraffin-soaked tissue into the container, and cooling to obtain paraffin blocks.
(4) And fixing paraffin blocks on a slicing machine, slicing according to the thickness standard of 3mm, putting the slices into warm water for flattening, rapidly picking up the slices by using a glass slide, and putting the slices on a slice baking machine at 45 ℃ for drying.
2. Immunohistochemical staining
(1) The tissue slices were placed in an oven at 65 ℃ for 1h, the slices were immersed in a1 x dewaxing/antigen retrieval solution, heated with a small fire in a microwave oven for 30min, cooled naturally to room temperature after the end, and washed with PBS for 3min.
(2) The cut pieces were added dropwise to 3%H 2O2 -covered tissue to block endogenous peroxidase, placed in a wet box, incubated at room temperature for 15min, and washed 3 times with PBS for 3min each.
(3) Removing water on the surface of the tissue, dripping goat serum for sealing, placing in a wet box, incubating for 30min at room temperature, and washing with PBS for 1 time and 3min.
(4) Tissue surface moisture was removed, primary antibody was diluted as indicated, added dropwise to the tissue surface, placed in a wet box and incubated overnight at 4 ℃.
(5) The wet box was removed and washed 3 times with PBS 3min at 37℃ Wen Xiangfu ℃30 min.
(6) Adding Polyperoxidase-anti-Mouse/Rabbit IgG dropwise, incubating at room temperature or 37 ℃ for 20-30 minutes, and washing with PBS for 3 times, each for 3 minutes
(7) Each slice was added with freshly prepared DAB chromogenic solution dropwise, observed under a microscope, and the positive signal was brown or tan, and after development, the reaction was stopped in PBS.
(8) Hematoxylin is dripped on the tissue, the tissue is stained for 30s, and the tissue is washed for 20min by tap water.
(9) The slices were respectively soaked in 70%,85%,95% absolute ethanol for 5min, and then in xylene for 10min. And finally, sealing the sheet with neutral resin.
2. As shown in fig. 5, the mice tumor tissue in example 4 was sectioned by paraffin embedding, immunohistochemical staining revealed that the combined treatment group had increased infiltration of cd8+ T cells (brown yellow positive cells), and increased cells secreting granzyme B, indicating that the combined treatment promoted the killing function of immune cells.
In conclusion, bortezomib promotes the killing function of T cells on lung squamous carcinoma cells in vitro. In an animal model, bortezomib can enhance the therapeutic effect of PD-1 monoclonal antibody, promote immune cell infiltration and enhance the killing activity of the immune cell infiltration. Therefore, the proteasome inhibitor bortezomib combined with the PD-1 monoclonal antibody can be used as a novel treatment mode of lung squamous carcinoma, and a novel strategy is provided for treating lung squamous carcinoma.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, or alternatives falling within the spirit and principles of the invention.

Claims (6)

1.用于治疗肺鳞癌的药物组合物,其特征在于,由蛋白酶体抑制剂与PD-1通路抑制剂组成。1. A pharmaceutical composition for treating squamous cell lung cancer, characterized in that it consists of a proteasome inhibitor and a PD-1 pathway inhibitor. 2.根据权利要求1所述的用于治疗肺鳞癌的药物组合物,其特征在于,所述蛋白酶体抑制剂为硼替佐米。2. The pharmaceutical composition for treating squamous cell lung cancer according to claim 1, wherein the proteasome inhibitor is bortezomib. 3.根据权利要求2所述的用于治疗肺鳞癌的药物组合物,其特征在于,所述PD-1通路抑制剂为PD-1单抗。3. The pharmaceutical composition for treating squamous cell lung cancer according to claim 2, wherein the PD-1 pathway inhibitor is a PD-1 monoclonal antibody. 4.根据权利要求3所述的用于治疗肺鳞癌的药物组合物,其特征在于,所述硼替佐米给药剂量0.75mg/kg/次,所述PD-1单抗给药剂量10mg/kg/次。4. The pharmaceutical composition for treating squamous cell lung carcinoma according to claim 3, characterized in that the dosage of bortezomib is 0.75 mg/kg/time, and the dosage of PD-1 monoclonal antibody is 10 mg/kg/time. 5.一种治疗肺鳞癌的药物,其特征在于,包含:a) 根据权利要求1-3中任一项所述的药物组合物;b) 药学上可接受的载体或辅料。5. A drug for treating squamous cell lung cancer, comprising: a) the pharmaceutical composition according to any one of claims 1 to 3; and b) a pharmaceutically acceptable carrier or excipient. 6.权利要求1-3任一所述的药物组合物在制备治疗肺鳞癌药物中的应用。6. Use of the pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a drug for treating lung squamous cell carcinoma.
CN202511223725.1A 2025-08-29 2025-08-29 Pharmaceutical composition for treating lung squamous carcinoma and application thereof Pending CN120733048A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202511223725.1A CN120733048A (en) 2025-08-29 2025-08-29 Pharmaceutical composition for treating lung squamous carcinoma and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202511223725.1A CN120733048A (en) 2025-08-29 2025-08-29 Pharmaceutical composition for treating lung squamous carcinoma and application thereof

Publications (1)

Publication Number Publication Date
CN120733048A true CN120733048A (en) 2025-10-03

Family

ID=97220789

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202511223725.1A Pending CN120733048A (en) 2025-08-29 2025-08-29 Pharmaceutical composition for treating lung squamous carcinoma and application thereof

Country Status (1)

Country Link
CN (1) CN120733048A (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140038959A1 (en) * 2011-08-12 2014-02-06 Genentech, Inc. Methods of treating tumors
CN107349191A (en) * 2017-08-10 2017-11-17 佛山市妇幼保健院 Application of the Vorinostat in the medicine for preparing treatment lung cancer
CN113750215A (en) * 2021-09-24 2021-12-07 暨南大学 Combination drugs used to treat tumors
CN117562999A (en) * 2023-11-10 2024-02-20 中国科学院合肥物质科学研究院 Application of Trp63 gene expression inhibitor in preparation of medicine for improving curative effect of squamous cell carcinoma immunotherapy
CN119950727A (en) * 2017-05-16 2025-05-09 能力制药公司 Drug combinations used to treat cancer

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140038959A1 (en) * 2011-08-12 2014-02-06 Genentech, Inc. Methods of treating tumors
CN119950727A (en) * 2017-05-16 2025-05-09 能力制药公司 Drug combinations used to treat cancer
CN107349191A (en) * 2017-08-10 2017-11-17 佛山市妇幼保健院 Application of the Vorinostat in the medicine for preparing treatment lung cancer
CN113750215A (en) * 2021-09-24 2021-12-07 暨南大学 Combination drugs used to treat tumors
CN117562999A (en) * 2023-11-10 2024-02-20 中国科学院合肥物质科学研究院 Application of Trp63 gene expression inhibitor in preparation of medicine for improving curative effect of squamous cell carcinoma immunotherapy

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANGELA M. DAVIES ET AL.: "Incorporating Bortezomib into the Treatment of Lung Cancer", CLINICAL CANCER RESEARCH, vol. 13, no. 15, 1 August 2007 (2007-08-01), pages 4647 - 4651 *
罗详冲 等: "程序性死亡受体1抑制剂卡瑞利珠单抗治疗老年性晚期肺鳞癌1例并文献复习", 中国医药科学, vol. 11, no. 16, 31 August 2021 (2021-08-31), pages 239 - 241 *

Similar Documents

Publication Publication Date Title
Li et al. Aiduqing formula inhibits breast cancer metastasis by suppressing TAM/CXCL1-induced Treg differentiation and infiltration
Li et al. Targeted inhibition of STAT3 induces immunogenic cell death of hepatocellular carcinoma cells via glycolysis
Sun et al. Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation
Duan et al. RIP3 knockdown inhibits necroptosis of human intestinal epithelial cells via TLR4/MyD88/NF-κB signaling and ameliorates murine colitis
He et al. Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy
US20190307794A1 (en) Method for inducing transdifferentiation of immune cells based on exosomes
Wang et al. Yu‐Ping‐Feng Formula Exerts Antilung Cancer Effects by Remodeling the Tumor Microenvironment through Regulating Myeloid‐Derived Suppressor Cells
Yu et al. B4GALNT2 gene promotes proliferation, and invasiveness and migration abilities of model triple negative breast cancer (TNBC) cells by interacting with HLA-B protein
Xu et al. Stereotactic body radiation therapy (SBRT) increases anti-PD-1 antitumor activity by enhancing the tumor immune microenvironment in mice with metastatic hepatocellular carcinoma
WO2024061385A1 (en) Use of selonsertib in preparation of drug for treating cancer
Jing et al. Recent advances in novel tumor immunotherapy strategies based on regulating the tumor microenvironment and immune checkpoints
Feng et al. Leptin acts on mesenchymal stem cells to promote chemoresistance in osteosarcoma cells
Li et al. Nitric oxide, a communicator between tumor cells and endothelial cells, mediates the anti-tumor effects of Marsdenia Tenacissima Extract (MTE)
Wu et al. Indole-3-carbinol inhibits PD-L1-mediated immune evasion in hepatocellular carcinoma via suppressing NF-κB p105 Ubiquitination
CN104069113B (en) Sldenafil application in the medicine of anti-angiogenic tumor is treated in preparation
Liu et al. Carbon ion irradiation combined with PD-1 inhibitor trigger abscopal effect in Lewis lung cancer via a threshold dose
CN120733048A (en) Pharmaceutical composition for treating lung squamous carcinoma and application thereof
Hao et al. Targeting HMGB1 modulates cancer-associated fibroblasts and enhances radiotherapy in lung adenocarcinoma
CN104083368B (en) G-1 application in terms of preparing three negative breast cancer targeted drugs based on g protein coupled receptor 30
CN116617359B (en) Application of semen vaccariae cyclic peptide B in preparing medicine for treating prostatic tumor
Wu et al. Effects of brucine on the OPG/RANKL/RANK signaling pathway in MDA‐MB‐231 and MC3T3‐E1 cell coculture system
CN102772806A (en) Application of micromolecular nucleic acid miR-302 for treating or preventing testicular cancer
CN111560433B (en) Application of human NUFIP1 and related products
CN114762730A (en) Application of PCSK9 in tumor immunotherapy and immune cell immune effect enhancement
Zhang et al. Tumor cell-derived microparticles containing MTX (MTX-TMPs) in the treatment of cholangiocarcinoma by modulating MDSCs

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination