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Anti-PD-L1/anti-LAG3 bispecific antibody and uses thereof

A bispecific antibody, PD-L1 technology, applied in the direction of antibody, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, anti-animal/human immunoglobulin, etc., can solve the death of infected mice rate increase, etc.

Active Publication Date: 2020-01-10
I MAB BIOPHARMA HANGZHOU CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

PD-L1 blockade (e.g. using blocking antibodies) leads to increased mortality in infected mice

Method used

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  • Anti-PD-L1/anti-LAG3 bispecific antibody and uses thereof
  • Anti-PD-L1/anti-LAG3 bispecific antibody and uses thereof
  • Anti-PD-L1/anti-LAG3 bispecific antibody and uses thereof

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example

[0267] Hereinafter, the present invention will be described in detail by way of examples.

[0268] The following examples are only intended to illustrate the invention and should not be construed as limiting the invention.

example 1

[0269] Example 1: Preparation of anti-PD-L1 monoclonal antibody

[0270] 1.1. Preparation and analysis of anti-human PD-L1 mouse monoclonal antibody

[0271] Anti-human PD-L1 mouse monoclonal antibody was generated using hybridoma technology.

[0272] Antigen: human PD-L1-Fc protein and CHOK1 cell line with high expression of human PD-L1 (PDL1-CHOK1 cell line).

[0273] Immunization: To generate mouse monoclonal antibody against human PD-L1, first use 1.5x 10 7 6-8 week old female BALB / c mice were immunized with PDL1-CHOK1 cells. On day 14 and day 33 after the first immunization, use 1.5x 10 7 The immunized mice were re-immunized with PDL1-CHOK1 cells. To select mice that produced antibodies that bound the PD-L1 protein, sera from immunized mice were tested by ELISA. Briefly, microtiter plates were coated with 1 μg / ml human PD-L1 protein in PBS overnight at 100 μl / well at room temperature (RT), and then blocked with 100 μl / well of 5% BSA. Dilutions of plasma from immuniz...

example 2

[0376] Example 2. Preparation of anti-LAG3 monoclonal antibody

[0377] 2.1. Screening of fully human monoclonal antibodies against LAG-3

[0378] Anti-LAG3 human monoclonal antibody (α-LAG-3 mAb) was generated by screening a fully human Fab phage display library. The wild-type LAG-3-ECD-huFc fragment can bind to Daudi cells, while the D1-D2 truncated LAG-3-ECD-huFc fragment cannot bind to Daudi cells ( Figure 21 ). Therefore, the D1-D2 domain is critical for LAG-3 function.

[0379] Antigens for phage display library panning. LAG-3 is a single-pass type I membrane protein that belongs to the immunoglobulin (Ig) superfamily and contains four extracellular Ig-like domains (ECD): domains (D)1, D2, D3 and D4. Expression of recombinant human LAG-3-ECD-human IgG1 (LAG-3-huFc) fusion protein or human D1-D2 truncated LAG-3-ECD-human IgG1 (ΔD1D2-LAG-3-huFc) fusion protein in 293T cells system.

[0380] Phage library. Ig gene segments in mammals are arranged in groups of variab...

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PUM

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Abstract

The invention provides an anti-PD-L1 / anti-LAG3 bispecific antibody, which can effectively block the interaction between PD-L1 and PD-1 and the interaction between LAG3 and a ligand (MHC II molecules,FGL1, etc.). The bispecific antibody is highly affinity to PD-L1 proteins (human PD-L1 protein, for example) and LAG3 proteins (human LAG3 protein, for example). The invention also provides an antibody and segment that has specificity on PD-L1 or LAG3 proteins; or an antibody and segment that has specificity on one or more other antigens.

Description

[0001] This application claims priority from PCT / CN2018 / 101547 filed on August 21, 2018 and PCT / CN2019 / 087943 filed on May 22, 2019, the contents of which are incorporated herein in their entirety. technical field [0002] The present invention relates to the field of antibodies, in particular to anti-PD-L1 / anti-LAG3 bispecific antibodies and uses thereof. Background technique [0003] Programmed death ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1), is a 40 kDa type 1 transmembrane protein believed to be involved in specific events ( Plays a major role in suppressing the immune system during, for example, pregnancy, tissue allografting, autoimmune diseases and other disease states such as hepatitis. The binding of PD-L1 to PD-1 or B7.1 transmits an inhibitory signal that reduces the proliferation of CD8+ T cells at the lymph nodes, and the recruitment of this PD-1 can also be further regulated by the gene Bcl-2 The lower regul...

Claims

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Application Information

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IPC IPC(8): C07K16/46A61K39/395A61P35/00A61P35/02A61P31/00C07K16/28C12N15/13
CPCC07K16/2827C07K16/2803A61P35/00A61P35/02A61P31/00C07K2317/24C07K2317/31A61K2039/505
Inventor 朴银英李良順郑义静金荣光金衍周朴泳燉李尙勋刘原圭郑在浩方磊蒋雯卿
Owner I MAB BIOPHARMA HANGZHOU CO LTD
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