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Homoharringtonine targeted therapeutic agent and application thereof

A technology of antigens and binding fragments, which is applied in the field of anti-cancer or tumor, the preparation of the above chemical products, CD79 antibody and its conjugate with homoharringtonine, which can solve the problem that monoclonal antibodies are limited and cannot meet the requirements of cancer and tumor Treatment needs and other problems, to achieve the effect of broad prospect of medicine

Active Publication Date: 2020-08-28
西安迪赛生物药业有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, among the CD79b-targeting antibodies disclosed in the prior art, the monoclonal antibodies with excellent effects are very limited and cannot meet the needs for the treatment of cancer and tumors

Method used

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  • Homoharringtonine targeted therapeutic agent and application thereof
  • Homoharringtonine targeted therapeutic agent and application thereof
  • Homoharringtonine targeted therapeutic agent and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 Preparation of CD79b monoclonal antibody of the present invention

[0024] According to the conventional hybridoma preparation method, using human CD79 protein (NCBI accession number of human CD79b gene sequence: NP_000617.1) as an antigen, hybridoma cells were produced by fusion of SP2 / 0 cells and immunologically collected lymphocytes, and multiple rounds of ELISA Screening and FACS screening finally selected a hybridoma cell line 79B6G7 with the best binding affinity of secreted antibody. The hybridoma cell 79B6G7 was cultured in a roller bottle incubator at 37°C for 10-15 days, and the supernatant was purified by Protein A affinity chromatography to obtain the mouse monoclonal antibody mAb79B6G7 of the present invention. After RNA extraction, amplification and sequencing identification, the amino acid sequence of the heavy chain variable region of the murine monoclonal antibody mAb79B6G7 is shown in SEQ ID NO: 1, wherein the amino acid sequences of HCDR1...

Embodiment 2

[0029] Example 2 Preparation of the conjugate of the present invention

[0030] Take 5.46mg of homoharringtonine, dissolve it in an appropriate amount of propylene glycol, and dilute to 1mL with water; add 0.76g of thiourea into 2ml of 6mol / L hydrochloric acid, heat to dissolve, cool to room temperature (24°C), and then mix with the above-mentioned homoharringtonine The ester-base solution was mixed for 20 minutes, then NaOH was added to adjust the pH to 9.0, and left to stand for 20 minutes, then hydrochloric acid was added to adjust the pH to 7.2, and the obtained reaction solution was set aside.

[0031] Take 5mg each of Polatuzumab, mAb79B6G7-scFv and hAb60H5 antibodies, dissolve them in 1ml PBS (pH7.2), add 0.1mL 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid sulfonic acid to each The DMSO solution of succinimide ester was mixed and allowed to stand at room temperature for 1 hour, then put into a dialysis bag, and dialyzed in PBS (pH7.2) at 4°C for 12 hours, and the o...

Embodiment 3

[0033] The research of embodiment 3 antitumor activity

[0034] The homoharringtonine conjugates of mAb79B6G7-scFv and hAb60H5 antibodies prepared according to Example 2 were used as experimental drugs, and the homoharringtonine conjugates of Polatuzumab antibodies were used as control drugs to study the antitumor effect of the drug of the present invention. active. The lymphoma BJAB cell line cultured on the RPMI1640 medium containing 10% fetal bovine serum was diluted with this medium to a concentration of 1*10 6 / mL, add sample to 96-well plate, 0.1mL per well, culture at 37°C for 24 hours, add 0.1mL of the above-mentioned medium without or each containing the above-mentioned drugs in gradient dilution, continue to cultivate for 72 hours, and then detect the cells in each well Quantity, calculate the half inhibitory concentration (IC 50 ). The results are shown in Table 2. Compared with the existing Polatuzumab antibody, the antibody of the present invention has signific...

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Abstract

The invention provides a novel anti-human CD79b monoclonal antibody and a conjugate of the monoclonal antibody and homoharringtonine, and the monoclonal antibody is used for resisting cancer or tumors. In addition, the invention further relates to a preparation method of the chemical product, a pharmaceutical composition, medical application and the like.

Description

technical field [0001] The invention belongs to the field of medicine and antibody technology, in particular, the invention relates to a novel CD79 antibody and its conjugate with homoharringtonine, which are used for anti-cancer or tumor. In addition, the present invention also relates to the preparation method, pharmaceutical composition and medical application of the above chemical products. Background technique [0002] Homocetaxine mepesuccinate (HHT for short) is an effective anti-cancer component extracted from the plant of the genus Haeruthus, which has a significant inhibitory effect on the growth of various cancer cell lines. It was approved by the Ministry of Health of my country as a commonly used anticancer drug as early as the 1990s. In recent years, its anticancer effect has also been recognized internationally. In 2012, the US FDA approved homoharringtonine injection (Synribo) for the treatment of chronic myelogenous leukemia. [0003] CD79b protein is a B-...

Claims

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Application Information

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IPC IPC(8): C07K16/28C12N15/13A61K39/395A61K47/68A61K31/55A61P35/00A61P35/02
CPCC07K16/2803A61K47/6803A61K31/55A61P35/00A61P35/02C07K2317/622C07K2317/56C07K2317/565C07K2317/92A61K2039/505C07K2317/24
Inventor 吴建中
Owner 西安迪赛生物药业有限责任公司
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