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Bispecific antibody specifically binding to gpnmb and cd3, and use thereof

A bispecific antibody and specific technology, applied in the direction of anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, specific peptide, drug combination, etc., can solve the problem of poor therapeutic effect and achieve high affinity and specific effect

Pending Publication Date: 2021-12-28
GREEN CROSS CORP THE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In cases where the cancer is in an early stage, its treatment may be by using these methods alone or in combination; however, in cases where the cancer is in an advanced stage, or where the cancer has spread through the blood to other tissues or has recurred Such an approach has a poor therapeutic effect in the case of

Method used

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  • Bispecific antibody specifically binding to gpnmb and cd3, and use thereof
  • Bispecific antibody specifically binding to gpnmb and cd3, and use thereof
  • Bispecific antibody specifically binding to gpnmb and cd3, and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Example 1. Production of anti-GPNMB / anti-CD3 bispecific antibody

Embodiment 11

[0067] Example 1.1. Selection of anti-GPNMB antibodies

[0068] In order to select GPNMB-specific antibodies, gene recombination technology was used to insert the DNA sequence to be expressed into the genome of a phage parasitic in Escherichia coli (E. coli). Then, using phage display technology, the inserted gene is expressed on the surface of the phage as a fusion to a phage coat protein.

[0069] Single colonies were collected from the final amplified population of the synthetic phage display scFv library. Subsequently, colonies were cultured in 1.5 mL of SB / carbenicillin at 37° C. and 220 rpm until the OD600 value reached about 0.8 to 1.0, and then cultured at 1 mMIPTG, 30° C. and 200 rpm for 12 hours or more. The reaction products were centrifuged at 5,500 rpm for 5 minutes, and then only the respective supernatants were added to the ELISA plate coated with the GPNMB antigen. Subsequently, the plate was reacted at room temperature for 2 hours, and washed 4 times with PB...

Embodiment 12

[0076] Example 1.2. Selection of anti-CD3 antibody

[0077] To select antibodies specific for human and monkey CD3, the mouse SP34 antibody was humanized and selected for antibodies that bind CD3 with various affinities. Among them, clone A15 consisting of the amino acid sequence of SEQ ID NO: 36 and clone E15 consisting of the amino acid sequence of SEQ ID NO: 41 were obtained. In addition, an antibody (Hu38E4.v1, manufactured by Genentech) having the amino acid sequence of SEQ ID NO: 40 was produced and used. In addition, for bispecific antibodies, anti-CD3 antibodies (Hu38, A15 or E15) were formed to have a knot-in-pore structure.

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Abstract

The present invention relates to a bispecific anti-GPNMB / anti-CD3 antibody specifically binding to CD3 and GPNMB, and the use thereof. Particularly, the bispecific antibody shows high affinity and specificity to CD3 and GPNMB and thus can induce death of cancer cells expressing GPNMB and inhibit proliferation thereof. Therefore, the bispecific antibody can be used as an effective therapeutic agent for cancers expressing GPNMB.

Description

technical field [0001] The present invention relates to a novel bispecific antibody specifically binding to GPNMB and CD3 and its use. Background technique [0002] Among the various causes of death, the frequent occurrence of death due to cancer accounts for the second largest proportion. Various methods for treating cancer have been continuously tried, and typical examples thereof include administration of anticancer agents, radiation, or surgical manipulation. In cases where the cancer is in an early stage, its treatment may be by using these methods alone or in combination; however, in cases where the cancer is in an advanced stage, or where the cancer has spread through the blood to other tissues or has recurred In some cases, such methods have poor therapeutic effect. [0003] Therefore, research on immune cell-based therapeutic techniques is attracting attention. Specifically, a technique is being developed in which immune cells taken from the patient's peripheral ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/30C07K16/28A61P35/00
CPCA61P35/00C07K16/30C07K2317/31C07K16/2809C07K2317/73C07K2317/74C07K2317/56C07K2317/565C07K2317/92C07K2317/52C07K2317/33C07K2317/622C07K2317/70
Inventor 朴在灿宋恩贞林昭贞李载哲权海奈李秀娥林玉宰金妏径赵显晶金吉重李智园金圣根元钟和张信娥
Owner GREEN CROSS CORP THE
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