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IgG (immunoglobulin) capable of treating cancers

A technology of immunoglobulin and pancreatic cancer, applied in the field of immunoglobulin, can solve the problem that the effect is not particularly good

Inactive Publication Date: 2015-10-14
张玲
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] There is an antibody against Trορ-2 in the prior art, but its effect is not particularly good, and there is still room for improvement to make its therapeutic effect better

Method used

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  • IgG (immunoglobulin) capable of treating cancers
  • IgG (immunoglobulin) capable of treating cancers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1 Obtainment of Modified Immunoglobulin for Treating Pancreatic Cancer

[0016] According to the light chain and heavy chain sequences 6 and 13 of the anti-Trop-2 antibody IgG disclosed in CN102827282A, the light chain and heavy chain sequences of the corresponding anti-Trop-2 antibody IgG were respectively obtained by nucleotide synthesis. The corresponding antibody was obtained by conventional protein expression methods in the field, named as Trop-2 b antibody.

[0017] According to the amino acid modification of the 6 CDR regions of the light chain and the heavy chain, nearly 50 different antibody variants were obtained respectively. Through activity screening, 16 antibody types with better anti-cancer effects were obtained. The CDR sequences are as follows :

[0018] VL: CDR1: SEQ ID NO: 1: GlnPheIleSerGlyTyr; or SEQ ID NO: 2: GlnPheIleSerAsnTyr;

[0019] CDR2: SEQ ID NO: 3: AlaSerSer;

[0020] CDR3: SEQ ID NO: 4: GlnGlnSerTyrSerThrAsnPheThr;

[0021] VH...

Embodiment 2

[0040] Example 2 Identification of fully human anti-Trop-2 antibody IgG with antigen recognition specificity

[0041] According to the method disclosed in CN102827282A, the IgG antibody obtained in the present invention can specifically bind to the Trop-2 positive cell BXPC3, but not to the NIH3T3 cell not expressing Trop-2. It shows that the antibody prepared by the present invention has better specificity.

Embodiment 3

[0042] Example 3 Effect of anti-Trop-2 antibody IgG on the proliferation of pancreatic cancer cell BXPC3

[0043] Dilute the anti-Trop-2 IgG antibody with DMEM culture solution, prepare the antibody at a concentration of 160mg / mL, add it to the 96-well culture plate cultured with BxPC3 cells and NIH3T3 cells, and culture for 3 days, and detect the proliferation of cells by MTS / PMS method . The results of MTS / PMS detection showed that there was no significant change in the inhibitory effect of the antibody on the proliferation of NIH3T3 cells that did not express Trop-2. Anti-Trop-2 antibody IgG was co-cultured with BXPC3 cells, and the antibody had a strong inhibitory effect on cell growth. The result is as follows:

[0044]

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Abstract

The invention provides IgG (immunoglobulin) capable of treating cancers and in particular relates to a humanized anti-Trop-2 (human trophoblast cell surface antigen 2) genetically engineered antibody IgG and an application thereof to treatment of pancreatic cancers. CDR (complementarity-determining region) sequences of the humanized anti-Trop-2 genetically engineered antibody IgG are amino acid sequences shown in SEQ ID NO.1-10. In vitro test results show that the anti-Trop-2 antibody IgG has obvious inhibiting effects on proliferation of pancreatic cancer cells. In vivo experiments of mice also prove that the anti-Trop-2 antibody IgG has better effects as well. IgG has better application prospects and application values.

Description

technical field [0001] The invention belongs to the biological field and relates to an immunoglobulin capable of treating cancer. Background technique [0002] Pancreatic cancer is an extremely dangerous malignant tumor. Its morbidity and mortality are on the rise all over the world. rate and death rate are almost equal. Diagnosis and treatment of pancreatic cancer is a world-class medical problem. It has high malignancy, rapid progression, strong invasiveness, early metastasis, poor prognosis, hidden symptoms, and is difficult to diagnose early. The characteristics determine that it is difficult to achieve radical resection by surgery. With the improvement of surgical methods and the introduction of comprehensive measures such as radiotherapy and chemotherapy, complications and mortality have been reduced, but the five-year survival rate is still less than 5%. Pancreatic cancer is a highly malignant tumor that has no satisfactory curative effect on existing treatment met...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/30A61K39/395A61P35/00
Inventor 张玲
Owner 张玲