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Antibody medicine conjugate of anti-CD30 antibody and lidamycin as well as preparation method and application thereof

An antibody drug, lidamycin technology, applied in botany equipment and methods, biochemical equipment and methods, antibody mimics/stents, etc., can solve problems such as toxic side effects, poor selectivity, and damage to normal cells

Active Publication Date: 2018-11-02
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although conventional radiotherapy and chemotherapy are highly effective for HL and ALCL, they are poor in selectivity. While killing tumor cells, they may also damage certain types of normal cells in the body, and often have obvious toxic and side effects, and the recurrence rate is high

Method used

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  • Antibody medicine conjugate of anti-CD30 antibody and lidamycin as well as preparation method and application thereof
  • Antibody medicine conjugate of anti-CD30 antibody and lidamycin as well as preparation method and application thereof
  • Antibody medicine conjugate of anti-CD30 antibody and lidamycin as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0120] Example 1. Preparation and properties of protein CD30-IgG-LDP in the antibody-drug conjugate of anti-CD30 antibody and lidamycin

[0121] 1. Construction of recombinant expression vector pIZDHL-IgG-LDP

[0122] The plasmid pIZDHL used in this example (Xiao-Yun Liu, et al. Chimetric, divalent and tetravalent anti-CD19monoclonal antibodies with potent in vitro and in vivoantitumor activity against human B-cell lymphoma and pre-B acutelymphoblastic leukemia cell lines.Int J Cancer, 2011, 129(2):497-506.) contains constant regions of antibody heavy and light chains. The LDP-VL gene of MluI-Kozac-SP-LDP-VL-BsiWI containing lidamycin prosthetic protein LDP and VL of anti-CD30 antibody shown in the 1-768 position of SEQ ID No.1 The fragment and the fragment of the VH gene containing the anti-CD30 antibody named XhoI-Kozac-SP-VH-NheI shown in the 1-426th position of SEQID No.3 were synthesized by Nanjing GenScript Biotechnology Co., Ltd., and passed OptimumGeneTM codon optimi...

Embodiment 2

[0147] Example 2. Antibody drug conjugate CD30-IgG-LDM of anti-CD30 antibody and lidamycin

[0148] 1. The protein CD30-IgG-LDP is assembled with AE to strengthen the ADC drug CD30-IgG-LDM

[0149] Take the pure product of lidamycin, separate the active chromophore through a hydrophobic column, the mobile phase is acetonitrile: water = 23%: 77% (volume ratio), detect the absorption peak at 340nm wavelength, and collect AE. Mix the protein CD30-IgG-LDP of Example 1 with the chromophore AE according to the molecular ratio (molar ratio) of 1:3, place on a shaker at 4°C in the dark and shake slowly for 12-16 hours to obtain the protein CD30-IgG - Boosted ADC drug CD30-IgG-LDM assembled by LDP and AE.

[0150] The mixture of the two was ultrafiltered with an ultrafiltration tube until there was no AE in the filtrate ( Figure 7 Middle A), indicating that free AE has been removed after protein fortification. The peak type of AE in the protein solution detected by HPLC ( Figure ...

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Abstract

The invention discloses an antibody medicine conjugate of an anti-CD30 antibody and lidamycin as well as a preparation method and application thereof. The antibody medicine conjugate provided by the invention is a medicine which couples anti-tumor antibiotic with an antibody, wherein the anti-tumor antibiotic is the lidamycin, and the antibody is the anti-CD30 antibody. The anti-CD30 antibody canbe IgG; the antibody medicine conjugate contains fusion protein with the name being LDP-light chain; the LDP-light chain contains a protein section with the name being LDP-VL; and the LDP-VL is a section which is obtained by connecting apoprotein of the lidamycin with a variable section of the light chain of the anti-CD30 antibody. The antibody medicine conjugate CD30-IgG-LDM which is obtained byassembling antibody fusion protein CD30-IgG-LDP and the lidamycin can be used for treating CD30 positive tumor (such as human hodgkin lymphoma or anaplastic large cell lymphoma).

Description

technical field [0001] The present invention relates to a class of antibody-drug conjugates capable of producing targeted tumor-killing effects in the technical field of medicinal proteins, a preparation method thereof and uses thereof, in particular to an antibody-drug conjugate of an anti-CD30 antibody and lidamycin, preparation thereof method and its use. Background technique [0002] Hodgkin lymphoma (Hodgkin lymphoma, HL) and anaplastic large cell lymphoma (anaplastic large cell lymphomas, ALCL) are malignant tumors originating from lymphocytes. Although conventional radiotherapy and chemotherapy are highly effective for HL and ALCL, they are poor in selectivity. While killing tumor cells, they may also damage some types of normal cells in the body, often causing obvious toxic and side effects, and high recurrence rate. [0003] CD30 is a member of the tumor necrosis factor receptor superfamily (tumor necrosis factor receptor superfamily, TNFRSF), which belongs to type...

Claims

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Application Information

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IPC IPC(8): A61K47/68A61K38/16C07K16/28C12N15/13C12N1/21C12N5/10C12R1/19
CPCA61K38/16C07K16/2878C07K2317/56C07K2319/00
Inventor 苗庆芳王蓉李良甄永苏张胜华李毅
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI