Pharmaceutical composition for treating tumors or cancers and application thereof

A composition and tumor technology, applied in drug combination, anti-tumor drug, pharmaceutical formula, etc., can solve the problems of narrow anti-tumor spectrum of oncolytic virus, low antibody efficiency, and inconclusiveness, so as to improve tracking and killing ability , Elimination of immunosuppressive response, simple and stable genome effect

Inactive Publication Date: 2020-08-07
FANTASIA BIOPHARMA ZHEJIANG CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

First, the anti-tumor spectrum of oncolytic viruses is relatively narrow: tumor cells that are sensitive to oncolytic viruses are accompanied by more viral replication: tumor cells that are not sensitive to oncolytic viruses are accompanied by less viral replication, so they need Screen out oncolytic virus strains with broad-spectrum sensitivity
Second, in vivo, viral replication is restricted over time and slowly cleared by the body
But at present: 1. The overall effective rate of PD-1 / PDL1 antibody treatment is not high. At present, the effective rate in melanoma and soft tissue sarcoma is about 30%, which is not a very high effective rate compared with traditional treatment.
At the same time, it is currently impossible to distinguish which patients will benefit from treatment
At present, the indicators that may predict the efficacy of the drug are tumor PD-L1 expression level and tumor mutation burden (TMB), but they are still inconclusive
2. Slow onset of effect: The median onset time of PD-1 antibody is 12 weeks. For 80% of patients who may be ineffective, if you wait until 12 weeks or more after PD-1 antibody treatment to adjust the treatment plan, there may be delays The optimal time for treatment, immune checkpoints are currently in the immunotherapy of tumors or cancers, and more effective treatment options and combination drugs developed thereby are still needed

Method used

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  • Pharmaceutical composition for treating tumors or cancers and application thereof
  • Pharmaceutical composition for treating tumors or cancers and application thereof
  • Pharmaceutical composition for treating tumors or cancers and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Cancer: Cancers treated according to the combinations described herein include, but are not limited to, leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, myeloblastic promyelocytic leukemia, myelomonocytic monocytic erythroleukemia, chronic leukemia , chronic myeloid (granulocytic) leukemia, chronic lymphocytic leukemia, mantle cell lymphoma, primary central nervous system lymphoma, Burkitt lymphoma and marginal zone B-cell lymphoma, polycythemia vera lymphoma, Chiggin's disease, non-Hodgkin's disease, multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain disease, solid tumors, sarcomas, and carcinomas, fibrosarcomas , myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, osteosarcoma, chordoma, angiosarcoma, endothelial sarcoma, lymphangiosarcoma, lymphangioendothelioma, synovium, mesothelioma, Ewing's tumor, leiomyosarcoma , rhabdomyosarcoma, colon sarcoma, colorectal cancer, pancreatic cancer, breast cancer, ovarian cancer, prostate can...

Embodiment 2

[0094] Example 2 To establish a subcutaneous transplanted lung cancer model, and compare the therapeutic effects of different mutant strains of viruses in lung cancer:

[0095] figure 2 A is the specific plan for intratumoral administration of oncolytic virus. As shown in the figure, after the tumor volume of lung cancer reaches at least 100mm3, intratumoral administration of oncolytic virus is given. The volume of intratumoral administration is 120ul, and the interval between administration is 1-2 days, depending on the original tumor growth rate. According to the above-mentioned administration flow chart, further in the mouse lung cancer tumor model, compare the therapeutic effect of different mutant strain viruses on lung cancer, figure 2 B shows the change in tumor volume of each tumor model mouse after administration of different mutant strains of virus. Further statistics show that compared with the wild-type virus U100, three mutant strains U200, U000 and U400 have i...

Embodiment 3

[0096] Example 3: Comparison of the killing ability of different viruses, especially U400, on tumor cells and the toxicity to normal cells: the in vitro killing of different mutant viruses on different cells was detected by the method of MTT detection.

[0097] The specific steps of the above detection method are as follows:

[0098] 1. Add (LLC / Hela / MC38 / MEF) cell suspension 100µl to each well of a 96-well culture plate to make the cell volume reach 1×10 4 1 / well, cultured at 37°C, 5% CO2 for 16 hours;

[0099]2. Dilute the viruses RV-WT (U100), RV-M51R (U200), RV-M51R-V221F-G226R (U400), RV-G21E-M51A-L111A-V221F (U000) to MOI (multiplicity of infection) respectively Inoculate 4 wells for each dilution gradient of 0.001, 0.01, 0.1, 1.0, 10, 100µl per well, and incubate at 37°C, 5% CO2 for 40h;

[0100] 3. Discard the supernatant in the 96-well culture plate, add fresh medium, and add MTT solution, 20 μL / well. Incubate at 37°C, 5% CO2 for 4 hours;

[0101] 4. Centrifuge th...

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Abstract

The invention relates to a pharmaceutical composition for treating tumors or cancers and application thereof, in particular to a pharmaceutical composition which comprises vesicular stomatitis virusesdelivered through direct injection or systemic administration or intratumoral delivery and is combined with PDL1 antibody intravenous administration to generate a synergistic effect in treatment of metastatic lung cancer. Besides, the oncolytic virus after gene mutation and the PDL1 antibody have the characteristic of recognizing tumor cells, normal cells are not damaged, and the oncolytic virusand the PDL1 antibody are sequentially combined for use to generate a synergistic effect in curative effect.

Description

technical field [0001] The invention belongs to the field of biotechnology, in particular, relates to the technical field of tumor or cancer combined immunotherapy. Background technique [0002] Malignant tumor is the main disease that causes human death, and the main treatment methods include surgery, radiotherapy and chemotherapy. Biological therapy is the fourth method developed in recent years and is known as the treatment of malignant tumors. It includes tumor vaccine therapy, tumor non-specific immunotherapy, antibody immunotherapy, cytokine therapy, adoptive cell immunotherapy, tumor gene therapy, etc. . Tumors arise from the accumulation of genetic and epigenetic changes in normal cells that drive the transformation of normal cells into malignancy. This complex pathological change process determines the diversity of mechanisms in the occurrence, maintenance and metastasis of different tumors. At present, surgical resection, chemotherapy and radiotherapy are common...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/766A61K39/395A61P35/00
CPCA61K35/766A61K39/395A61P35/00A61K2300/00
Inventor 秦晓峰吴飞
Owner FANTASIA BIOPHARMA ZHEJIANG CO LTD
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