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An immune checkpoint inhibitor for cancer therapy

An immune checkpoint and cancer treatment technology, applied in the direction of immunoglobulin, drug combination, peptide, etc., can solve problems such as tumor recurrence

Active Publication Date: 2022-04-19
北京加美康联医疗科技有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, although immune checkpoint inhibitors can temporarily reactivate CTLs and enhance tumor control, if effector memory T cells are impaired, the clinical response may fade, leading to acquired resistance or tumor recurrence after drug discontinuation

Method used

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  • An immune checkpoint inhibitor for cancer therapy
  • An immune checkpoint inhibitor for cancer therapy
  • An immune checkpoint inhibitor for cancer therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Obtaining novel ILDR2 chimeric antibodies

[0026] For mouse immunization, 6- to 8-week-old female BALB / c mice (purchased from Shanghai Jiake Biotechnology Co., Ltd.) were used as experimental animals, and 50 μg of human ILDR2 protein (purchased from Beijing Yiqiao Shenzhou Biotechnology Co., Ltd.) was used for the first immunization Mix well with complete Freund's adjuvant to form an emulsion, inject 0.5ml / mouse intraperitoneally into mice, and carry out booster immunization every 2 weeks, use 25 μg of human ILDR2 protein to fully mix with incomplete Freund's adjuvant to form an emulsion for booster immunization, Inject 0.5ml / mouse intraperitoneally into the mouse, boost immunization 3 times, take the venous blood of the mouse and separate the serum one week after the last immunization, measure the titer of the obtained antibody by ELISA method, and select the mouse cells with high titer to prepare Single splenocyte suspensions were prepared from hybridomas....

Embodiment 2

[0031] Example 2: Detection of anti-human ILDR2 chimeric monoclonal antibody

[0032] Detect the kinetic constant of the anti-human ILDR2 chimeric monoclonal antibody (hereinafter referred to as Anti-ILDR2-M) obtained in Example 1 and its antigen binding, and use the instrument optical surface plasmon resonance technology to detect the molecules coupled and coated on the biochip Binding and dissociation with the analyte molecule. Specifically, Anti-ILDR2-M was dissolved in a sodium acetate buffer solution (pH 5.0) and coupled to a CM chip, followed by blocking with 1M ethanolamine. In the binding phase, different concentrations of Anti-ILDR2-M were injected at a speed of 30 μL / min for 3 min, and in the dissociation phase, PBS buffer solution was injected at a speed of 30 μL / min for 10 min, and the binding kinetic constant and dissociation kinetic constant were passed Biacore3000 software was used for analysis and calculation. The binding kinetic constants, dissociation kinet...

Embodiment 3

[0037] Example 3: Preparation of novel humanized ILDR2 antibody

[0038] The humanized form of anti-human ILDR2 antibody was prepared by referring to the preparation method of Molecule Immunol, and the humanized template that best matched the Anti-ILDR2-M non-CDR region was selected from the Germline database, and the template of the heavy chain variable region was human IgVH4-28*03, the template of the variable region of the light chain is human IGKV1-16*02, the CDR region of the mouse antibody is grafted onto the selected humanized template, and the CDR region of the human template is replaced to obtain the heavy chain of the humanized antibody For the variable region, the amino acid sequence is shown in SEQ ID NO:7, and the light chain variable region of the humanized antibody is obtained, and the amino acid sequence is shown in SEQ ID NO:8. The amino acid sequence (VH) of the variable region of the heavy chain (VH) and the amino acid sequence (VL) of the variable region of...

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Abstract

The present invention protects an immune checkpoint inhibitor for cancer treatment. In particular, the present invention provides a monoclonal antibody, which is a humanized monoclonal antibody that can specifically bind to ILDR2 Combined with ILDR2, it can effectively inhibit the immune function of ILDR2, and has the function of inhibiting tumor progression.

Description

technical field [0001] The present invention relates to the field of immune checkpoint inhibitors, in particular to an immune checkpoint inhibitor for cancer treatment. Background technique [0002] mAbs targeting co-inhibitory immune checkpoints, such as PD-1 and CTLA-4, have shown clinical activity in a variety of malignancies, including melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer, Head and neck squamous cell carcinoma, MSI-high colorectal cancer, Merkel cell carcinoma, and Hodgkin lymphoma, and has transformed medical oncology practice. [0003] In particular, immune checkpoint inhibitors have been successful in the treatment of melanin, with approved regimens including anti-PD-1 (nivolumab and pembrolizumab), anti-CTLA-4 (ipilimumab) and anti-PD-1 / CTLA-4 combination regimens (nivolumab-ipilimumab). [0004] At present, experts have more and more experience in the treatment of various malignant tumors with "immune checkpoint inhibitors", a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/395A61P35/00A61P35/02
CPCC07K16/2803A61P35/00A61P35/02C07K2317/565C07K2317/24A61K2039/505
Inventor 蒋可
Owner 北京加美康联医疗科技有限责任公司
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