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CD137 antibody and application thereof

A CD137, antibody technology, applied in the field of biomedicine, can solve the problems of limited specific recognition and binding ability, limited ability of immune cells to secrete cytokines, limited ability to activate, etc.

Active Publication Date: 2019-07-12
SHANGHAI ORIGINCELL MEDICAL TECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, currently developed CD137 antibodies have limited ability to specifically recognize and bind CD137 protein, have limited ability to activate NF-κB signaling pathway, have limited ability to promote PBMC cell proliferation, and / or have limited ability to induce immune cells to secrete cytokines. There is an urgent need to develop new CD137 antibodies for new drug development

Method used

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  • CD137 antibody and application thereof
  • CD137 antibody and application thereof
  • CD137 antibody and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0165] 1 antibody or antigen-binding fragment thereof in 1 x 10 -9 K below M D Values ​​are combined with CD137 protein.

[0166] 2. The antibody or antigen-binding fragment thereof according to embodiment 1, whose titer when binding to CD137 protein is 1:10 4 or higher.

[0167] 3. The antibody or antigen-binding fragment thereof according to any one of embodiments 1-2, which competes with the CD137 ligand for binding to the CD137 protein.

[0168] 4. The antibody or antigen-binding fragment thereof according to any one of embodiments 1-3, which activates the NF-κB signaling pathway.

[0169] 5. The antibody or antigen-binding fragment thereof according to embodiment 4, wherein the activating the NF-κB signaling pathway comprises up-regulating the expression level of the NF-κB luciferase reporter gene.

[0170] 6. The antibody or antigen-binding fragment thereof according to any one of embodiments 1-5, which promotes PBMC cell proliferation.

[0171] 7. The antibody or a...

Embodiment 1

[0247] The preparation of embodiment 1 antibody

[0248] Mouse immunization: balb / c mice were immunized 5 times with Freund's adjuvant (sigma) mixed with 50 μg human CD137 extracellular domain protein (purchased from Beijing Yiqiao Shenzhou Science and Technology Co., Ltd.) via intraperitoneal (i.p.) and subcutaneous (s.c.) . Prior to fusion, mice were boosted intraperitoneally with the same amount of antigen. Serum titers (titers) of anti-human CD137 antibodies from splenocytes of immunized mice reached 10 5 , splenocytes from immunized mice were fused with mouse myeloma cells SP2 / 0 according to standard methods.

[0249] Hybridoma fusion: fusion of mouse spleen according to the existing conventional hybridoma fusion method, and HAT screening method to screen the fused hybridoma cells. The supernatant was taken and detected by ELISA with a human CD137-his-tag antigen-coated microtiter plate. Positive hybridoma clones were selected and expanded in 24-well plates and subclo...

Embodiment 2

[0251] Determination of Example 2 Antibody Sequence

[0252] Use TrizoI (purchased from Shanghai Sangong Bio) to extract the total RNA of the hybridoma cell line prepared in Example 1, use a reverse transcription kit (purchased from Takara Company) to reverse-transcribe the mRNA into cDNA, and use the cDNA as a template for PCR. The Ig-PrimerSets kit clones the antibody heavy chain and light chain variable region sequences respectively; the cloned antibody heavy chain and light chain variable region sequences are sequenced.

[0253] The antibodies sequenced were named c2H10, c3F3, c3F10, c20A11, c34F2, c9A7, c6F5 and c8G6, respectively. These monoclonal antibodies were constructed into chimeric antibodies: the heavy chain variable region and light chain variable region of each antibody were cloned into the heavy chain expression vector and the light chain expression vector respectively, and the heavy and light chain expression vectors of each chimeric antibody were cloned into...

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Abstract

The invention relates to an antibody or an antigen-binding fragment thereof that binds to a CD137 protein with a KD value of 1*10<-9> M or less. The antibody or the antigen-binding fragment thereof has strong specific recognition and binding ability to the CD137 protein, and can activate a NF-[kappa]B signaling pathway, promote the proliferation of PBMC cells and / or induce immune cells to secretecytokines. The invention also provides an application of the antibody or the antigen-binding fragment thereof in preparation of drugs for treatment or prevention of cancer or autoimmune diseases.

Description

technical field [0001] This application relates to the field of biomedicine, in particular to a CD137 antibody and its application. Background technique [0002] CD137 (CD137 / TNFRSF9) was the first TNFRSF member identified as a possible immunotherapeutic target. In addition to activated NK and NKT cells, CD137 is constitutively expressed by regulatory T cells (Treg) and several innate immune cell populations, including DCs, mast cells, monocytes, neutrophils and eosinophils. CD137 mediates activation of behavioral TNF receptor-associated factors 1 and 2 (TRAF1 and TRAF2) and nuclear factor kappa B (NF-κB), a master transcription factor that regulates immune cell function, through association. In T cells, after the CD137 ligand acts on CD137, it transmits signals to the cell through TRAF2 (Tumor necrosis factor receptor-associated factor 2), TRAF1 and MAPK, and participates in T cell activation. Activation, cytokine secretion, and regulation of monocyte proliferation and di...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C12N15/13A61K39/395A61P35/00A61P37/02
CPCA61K2039/505A61P35/00A61P37/02C07K16/2878C07K2317/24C07K2317/34C07K2317/56C07K2317/565C07K2317/73C07K2317/75C07K2317/92
Inventor 郭昊马海立黄勇何妍王华菁李博华杨焕凤何晓文
Owner SHANGHAI ORIGINCELL MEDICAL TECHNOLOGY CO LTD
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