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Pharmaceutical composition for synergistically enhancing anti-HER2 positive tumor effect

An anti-tumor and tumor technology, applied in the field of biomedicine, can solve the problems of high toxicity and side effects, cost, and high development costs, and achieve the effect of inhibiting tumor growth

Pending Publication Date: 2019-12-03
ANHUI PROVINCIAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, the drug treatment of malignant tumors is mainly based on chemical drugs and targeted therapy drugs, which are expensive to develop, and high doses of toxic and side effects are often unbearable for patients
Clinical studies have shown that the cost of developing a cancer drug is billions of dollars, and the process from theory to FDA approval takes 15 years

Method used

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  • Pharmaceutical composition for synergistically enhancing anti-HER2 positive tumor effect
  • Pharmaceutical composition for synergistically enhancing anti-HER2 positive tumor effect
  • Pharmaceutical composition for synergistically enhancing anti-HER2 positive tumor effect

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1, HuA21 antibody, trastuzumab, meclofenamic acid and derivatives thereof

[0057] 1. Antibody to HuA21

[0058] The HuA21 antibody used in the present invention is prepared according to the following method:

[0059] 1. The recombinant expression vector pSectag2A(Zeo+) / HuA21-H used to express the heavy chain of the HuA21 antibody: replace the nucleotide sequence shown in SEQ ID No.5 with the nucleoside between the SfiI and KpnI sites in the pSectag2A(Zeo+) vector acid sequence, keeping other sequences of pSectag2A(Zeo+) unchanged, the resulting recombinant vector was named pSectag2A(Zeo+) / HuA21-H.

[0060] 2. Recombinant expression vector pSectag2A(Zeo+) / HuA21-L for expressing the light chain of the HuA21 antibody: replace the nucleotide sequence shown in SEQ ID No.6 with the nucleoside between the SfiI and KpnI sites in the pSectag2A(Zeo+) vector acid sequence, keeping other sequences of pSectag2A(Zeo+) unchanged, the resulting recombinant vector was named p...

Embodiment 2

[0073] Example 2. The combined use of anti-HER2 humanized antibody and meclofenamic acid can effectively inhibit the proliferation of tumor cells

[0074] CCK-8 method was used to detect the ability of humanized antibody HuA21 and trastuzumab alone or in combination with meclofenamic acid ethyl ester (MA2) to inhibit tumor cell proliferation in vitro. The experiment was repeated three times, and the steps of each repeated experiment were as follows:

[0075] BT-474 breast cancer cells with high expression of HER2 were cultured in vitro (Shanghai Cell Bank, Chinese Academy of Sciences). BT-474 breast cancer cells were trypsinized and inoculated in 96-well cell culture plates (Corning Company), each well contained 2 × 10 3 Each well of the culture plate has 100 μL of RPMI1640 medium containing 10% special grade fetal bovine serum, in CO 2 After culturing in the incubator for 24 hours, the medium was replaced with RPMI1640 fresh medium containing humanized antibody HuA21 and 10...

Embodiment 3

[0085] Example 3. Combination of anti-HER2 humanized antibody and meclofenamic acid can effectively inhibit tumor growth

[0086] PBS was used to dissolve the humanized antibody HuA21 and trastuzumab in Example 1, and DMSO was used to dissolve MA2 to obtain a HuA21 solution with a concentration of 2 mg / mL and a trastuzumab solution with a concentration of 2 mg / mL. HuA21 concentration is 2mg / mL and MA2 concentration is 2mmol / L HuA21 and MA2 mixed solution, trastuzumab concentration is 2mg / mL and MA2 concentration is 2mmol / L trastuzumab and MA2 mixed solution, antibody total A mixed solution of trastuzumab and HuA21 at a concentration of 2 mg / mL (1 mg / mL each of HuA21 and trastuzumab), and a concentration of HuA21 of 2 mg / mL and a concentration of trastuzumab of 2 mg / mL and a concentration of MA2 It is a mixed solution of 2mmol / L HuA21, trastuzumab and MA2.

[0087] Take 42 5-6-week-old BalB / C female nude mice (Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.), an...

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Abstract

The invention discloses a pharmaceutical composition for synergistically enhancing an anti-HER2 positive tumor effect. The invention provides an anti-tumor composition. The anti-tumor composition is composed of an anti-HER2 humanized antibody and meclofenamic acid. The old drug of meclofenamic acid and the humanized anti-tumor antibody drug are combined for use according to a certain proportion, so that the dosage of each drug can be greatly reduced, the toxic and side effects can be reduced, the drug effect can be remarkably enhanced, and the drug resistance of tumor cells can be overcome. The synergistic drug combined cocktail drug therapy has a wide prospect in tumor treatment.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a drug combination that synergistically enhances the anti-HER2 positive tumor effect. Background technique [0002] Trastuzumab (Herceptin, English name Trastuzumab / Herceptin) is an anti-human epidermal growth factor receptor 2 (human epidermal growth factor receptor-2, HER2) humanized monoclonal antibody drug developed by Genetech, FDA of the United States Approved for marketing in 1998, trastuzumab combined with chemotherapy drugs (paclitaxel, etc.) has become the first-line treatment for HER2 overexpressed advanced metastatic breast cancer and advanced gastric cancer. In 2012, the U.S. FDA approved another anti-HER2 humanized monoclonal antibody drug Pertuzumab (English name Pertuzumab / Perjeta) from Genetech to be listed. Pertuzumab combined with trastuzumab and chemotherapy drugs can Further improve the clinical treatment effect of HER2 overexpression advanced metastatic breast ca...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P35/00A61K31/196
CPCA61K39/39558A61K31/196A61P35/00A61K2300/00
Inventor 沈国栋程联胜胡世莲刘兢杨留洋
Owner ANHUI PROVINCIAL HOSPITAL
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