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Multispecific antibody targeting HIV gp120 protein and human CD3 molecule and application thereof

A multi-specific antibody and specific technology, applied in the field of immunoglobulin, can solve the problem of inability to completely remove HIV, and achieve the effect of reducing the load of virus and virus pool

Active Publication Date: 2022-06-07
珠海臻谱基因科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, none of the programs used clinically to treat AIDS can completely eliminate HIV from the patient's body, and the patient needs to take medicine for life

Method used

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  • Multispecific antibody targeting HIV gp120 protein and human CD3 molecule and application thereof
  • Multispecific antibody targeting HIV gp120 protein and human CD3 molecule and application thereof
  • Multispecific antibody targeting HIV gp120 protein and human CD3 molecule and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] Embodiment 1. Construction and expression of recombinant vector of multispecific antibody HIV-DNS

[0078] 1. Structure of the multispecific antibody HIV-DNS

[0079] (1) Schematic diagram of the multispecific antibody HIV-DNS structure figure 1 shown

[0080] The light chain variable region of the HIV-DNS multispecific antibody molecule adopts the HIV virus receptor, domain 1 of the human T cell surface glycoprotein CD4 molecule (https: / / www.uniprot.org / uniprot / P01730, Domain 1 of humanT-cell surface glycoprotein CD4, CD4-D1), this domain is the primary receptor for human immunodeficiency virus-1 (HIV-1) that HIV virus binds to human CD4+ cells and can bind to HIV gp120 protein .

[0081] The light chain constant region of HIV-DNS adopts human immunoglobulin Kappa light chain constant region (humanImmunoglobulin kappa chain constant region, IGKC, https: / / www.uniprot.org / uniprot / P01834).

[0082] In the heavy chain of the anti-gp120 HIV-DNS multispecific antibody mo...

Embodiment 2

[0123] Example 2. Detection of the binding capacity of HIV-DNS and HIV gp120 glycoprotein by ELISA

[0124] Commercially purchased recombinant HIV gp120 glycoprotein (purchased from Abcam, Cat. No. 174070) was diluted with coating solution to 1.0 ug / ml, and coated on ELISA plate at 100 ng / well, overnight at 4°C. Afterwards, 2% BSA in PBST solution was added to each well and incubated for 1.5-2 hours. During the incubation period, the blocking solution was diluted to a final BSA concentration of 0.5% BSA with PBST, which was used as the antibody diluent to double-dilute the multispecific antibody HIV-DNS, starting at 10 ug / ml and ending at 1.25 pg / ml. Human IgG (Shanxi Kangbao Biological Products Co., Ltd.) was used as reference substance 1, and HIV-TS with the same target was used as reference substance 2. After the ELISA plate is blocked, wash thoroughly. Add doubling dilution of each antibody, 100 ul / well, incubate at 37 °C for 1 hour, after thorough washing, add 100 ul of...

Embodiment 3

[0126] Example 3. Surface plasmon resonance (SPR) method to detect the affinity of HIV-DNS for recombinant gp120

[0127] The measuring instrument used Biacore X100 of GE. Amine coupling kit, human antibody capture kit, CM5 chip and 10×HBS-EP pH7.4 and other related reagents and consumables were purchased from GE Healthcare.

[0128] The affinity of the multispecific antibody HIV-DNS was determined by the capture method. When measuring the affinity of the HIV-DNS multispecific antibody purified and prepared in step (3) of Example 1 for gp120, the anti-Fc antibody was coupled to the surface of the CM5 chip, and the HIV-DNS was diluted to an appropriate concentration, and the CM5 was captured separately. The surface of the chip was used as the stationary phase, and the recombinant gp120-His (purchased from Abcam, Item No. ab174070) was set up to flow through the stationary phase surface in a single-cycle method with a series of concentration gradients at a flow rate of 30ul / min...

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Abstract

The invention discloses a multispecific antibody targeting HIV gp120 protein and human CD3 molecule and application thereof. The multispecific antibody includes an antibody specifically binding to gp120 and a single-chain antibody specifically binding to CD3 whose amino acid sequence is 471-710 of sequence 1, and the antibody specifically binding to gp120 includes an amino acid sequence of 1-710 of sequence 1. The heavy chain variable region at position 136 and the amino acid sequence are the light chain variable region at positions 1-125 of Sequence 3, and the single-chain antibody is fused to the C-terminus of the heavy chain of an antibody specifically binding to gp120. The multispecific antibody targets different epitopes of gp120, which can significantly improve the neutralization effect of HIV virus, reduce the probability of virus escape mutation, and target CD3 molecules to better eliminate the virus and improve the clinical efficacy of antibody therapy.

Description

technical field [0001] The present invention relates to the field of immunoglobulin, in particular to a multispecific antibody targeting HIV gp120 protein and human CD3 molecule and its application. Background technique [0002] Acquired Immune Deficiency Syndrome (AIDS), also known as AIDS, is caused by infection with Human Immunodeficiency Virus (HIV). HIV can destroy the human immune system, the most important CD4 in the human immune system + T lymphocytes as the main target of attack, a large number of destruction of the cells, so that the body loses immune function. Therefore, the human body is easily infected with various diseases, and malignant tumors can occur, and the mortality rate is high. HIV invades CD4 + When T cells are used, the CD4 molecule on the cell surface is the main receptor, and CCR5 or CXCR4 is the coreceptor. In the first step of infection, the virus gets close to the cell through the binding of its outer membrane protein gp120 to the CD4 molecu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/46C12N15/13C12N15/85C12N5/10A61K39/42A61P31/18
Inventor 胡显文李磊焦长乐袁盛凌廖翔范泰漓杨立宪刘紫龙袁建军杜滨胡嘉琪王延明
Owner 珠海臻谱基因科技有限公司
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