Unlock instant, AI-driven research and patent intelligence for your innovation.

Method and drug combination for treating disease with anti-tigit antibody combined with PD-1 inhibitor

A technology of PD-1 and inhibitors, applied in drug combinations, antibody medical components, antibodies, etc., can solve problems such as disappearance

Active Publication Date: 2022-07-26
JIANGSU HENGRUI MEDICINE CO LTD +1
View PDF33 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Chew et al. found that the combination of TIGIT antibody and PD-1 antibody can promote the killing function of CD8 T cells against HIV and melanoma, but this effect disappears with the blockade of CD226 (Chew, Fujita et al.2016)

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method and drug combination for treating disease with anti-tigit antibody combined with PD-1 inhibitor
  • Method and drug combination for treating disease with anti-tigit antibody combined with PD-1 inhibitor
  • Method and drug combination for treating disease with anti-tigit antibody combined with PD-1 inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0174] Example 1. Preparation of TIGIT antigen antibody

[0175] 1.1 Protein design and expression

[0176] Using human TIGIT protein (Uniprot No.: Q495A1) as the template of TIGIT of the present disclosure, the amino acid sequences of the antigen and detection protein of the present disclosure were designed, and different tags were optionally fused on the basis of the TIGIT protein, and cloned into the pHr carrier ( Self-produced) or pXC-17.4 vector (LONZA), transiently expressed in 293 cells or stably expressed in CHO cells and purified to obtain the antigens and detection proteins encoding the disclosure. The following TIGIT antigens without special instructions refer to human TIGIT.

[0177] Fusion protein of TIGIT extracellular domain and mouse IgG2aFc fragment: TIGIT-mFc for immunization and detection

[0178] MEFGLSWLFFLVAILKGVQC MMTGTIETTGNISAEKGGSIILQCHLSSTTAQVTQVNWEQQDQLLAICNADLGWHISPSFKDRVAPGPGLGLTLQSLTVNDTGEYFCIYHTYPDGTYTGRIFLEVLESSVAEHGARFQIPEPRGPTIKPCPPCKCPAP...

Embodiment 2

[0197] Example 2. Preparation of anti-human TIGIT hybridoma monoclonal antibody

[0198] 2.1 Immunization

[0199] Anti-human TIGIT monoclonal antibodies were produced by immunizing mice. SJL white mice were used in the experiment, female, 6-8 weeks old (Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd., animal production license number: SCXK (Beijing) 2012-0001). Breeding environment: SPF grade. After the mice were purchased, they were reared in a laboratory environment for 1 week, regulated by a 12 / 12 hour light / dark cycle, the temperature was 20-25°C, and the humidity was 40-60%. The acclimated mice were immunized according to the following protocol. The immunizing antigen was the extracellular region of human TIGIT with mFc (SEQ ID NO: 1).

[0200] Immunization regimen: with Gold Adjuvant (Sigma Cat No.T2684) with Thermo Alum (Thermo Cat No. 77161) adjuvant cross-immunization. Antigen and adjuvant ( Gold Adjuvant) ratio of 1:1, antigen and adjuvant (T...

Embodiment 3

[0242] Example 3. Humanization of murine anti-human TIGIT antibody

[0243] By comparing the IMGT human antibody heavy and light chain variable region germline gene database with MOE software, the heavy chain and light chain variable region germline genes with high homology to the mouse antibody were selected as templates, and the murine antibody's germline genes were selected as templates. The CDRs were grafted into corresponding human templates to form variable region sequences in the order of FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. If necessary, back-mutate the amino acids in the FR region to obtain a humanized anti-TIGIT monoclonal antibody. In the following exemplary embodiments, the determination of amino acid residues in the CDR regions is determined and annotated by the Kabat numbering system.

[0244] The light and heavy chain variable regions of the above murine antibodies are linked with the light and heavy chain constant regions of human antibodies to form a chimeric anti...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present disclosure relates to methods and pharmaceutical combinations for treating diseases with anti-TIGIT antibodies in combination with PD-1 inhibitors. Further, the present disclosure relates to a drug of an anti-TIGIT antibody or an antigen-binding fragment thereof in combination with a PD-1 inhibitor (eg, an anti-PD-1 antibody) to treat human TIGIT-related diseases (eg, tumors).

Description

technical field [0001] The present disclosure relates to methods and pharmaceutical combinations for treating diseases with anti-TIGIT antibodies in combination with PD-1 inhibitors. Background technique [0002] The statements herein merely provide background information related to the present invention and do not necessarily constitute prior art. [0003] In recent years, immune checkpoint therapy targeting immune cell co-inhibitory receptors has made great progress in tumor immunotherapy, and the discovery and validation of new co-inhibitory receptors has become a global competitive hotspot. T cells are key mediators of immune responses, and their activation depends on TCR signaling and costimulatory signals. Costimulatory signals are the limiting signals of T cell activation, and their dysfunction is involved in the occurrence of autoimmune diseases (Immunol Rev, 2012, 248: 122-139; Autoimmun Rev, 2013, 12: 1171-1176). TIGIT (T cell immunoglobulin and ITIM domain) is a...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K39/395A61P35/00A61P35/02A61P37/02A61P31/00C07K16/28
CPCA61K45/06A61K39/39533A61P35/00A61P35/02A61P37/02A61P31/00C07K16/2803A61K2039/507C07K2317/56C07K2317/565C07K2317/24C07K2317/92C07K2317/76A61K2300/00
Inventor 付雅媛许志宾陶维康
Owner JIANGSU HENGRUI MEDICINE CO LTD