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Nanometer aptamer for multispecific antibody delivery as well as application and construction method of nanometer aptamer

A multi-specific antibody and construction method technology, which is applied in the field of nano-adapters for multi-specific antibody delivery, can solve the problems of affecting the antigen-binding ability of antibodies, complex administration methods, and short half-life, etc., and achieve good clinical transformation prospects, Effect of enhanced anti-tumor ability and simple structural design

Active Publication Date: 2021-02-09
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although bispecific / multispecific antibodies can greatly improve the titer and disease treatment effect of antibodies through double or multiple recognition, their structural design is more complex, and the complexity of the design, preparation, and purification processes is higher than that of monoclonal antibodies. It has increased significantly, and most of them are prepared by chemical coupling and DNA recombination technology, which requires chemical modification of the effective monoclonal antibody, which will inevitably affect the antigen-binding ability of the antibody itself, and also has a short half-life and complicated administration methods. , poor stability, poor solubility, high cost and other disadvantages, there is currently no bispecific / multispecific antibody approved for the treatment of solid tumors

Method used

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  • Nanometer aptamer for multispecific antibody delivery as well as application and construction method of nanometer aptamer
  • Nanometer aptamer for multispecific antibody delivery as well as application and construction method of nanometer aptamer
  • Nanometer aptamer for multispecific antibody delivery as well as application and construction method of nanometer aptamer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Example 1 Construction and Characterization of Nano-Aptamer αFc-NP

[0086] Raw material source and processing method used in the embodiment:

[0087] Goat anti-rat IgG Fc fragment antibody was purchased from Rockland Company, the United States;

[0088] Amino-functionalized polystyrene microspheres (25-300nm), purchased from Shanghai McLean Biochemical Technology Co., Ltd.;

[0089] Sodium Periodate (NaIO 4 ), ready-to-use and ready-to-use, avoid light (purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., China);

[0090] Sodium borohydride, ready-to-use and ready-to-use (purchased from Sarn Chemical Technology (Shanghai) Co., Ltd., China);

[0091] Purpald solution: 10 mg / mL 4-amino-3-hydrazino-5-mercapto-1,2,3-triazole (purchased from Bailingwei Technology Co., Ltd.), dissolved in 1N NaOH. Prepared before use. It reacts with aldehyde groups and becomes purple after the action of sodium periodate (Purpald: 4-amino-3-hydrazino-5-mercapto-1,2,4-triazol...

Embodiment 2

[0119] Example 2, Application of Double Multispecific Nanobodies

[0120] Both the mouse B16-F10 melanoma cell line and the mouse 4T1 orthotopic breast cancer cell line were obtained from the American Standard Biological Collection (ATCC). SPF grade female C57BL / 6 mice and female BALB / C mice, 5-6 weeks old, were purchased from Hunan Slake Jingda Experimental Animal Co., Ltd. The mice were kept in the Experimental Animal Center of South China University of Technology, and the animal experiment procedures followed the relevant provisions of the South China University of Technology's Regulations on the Management of Experimental Animals.

[0121] Rat anti-mouse PD1 (CD279) antibody (αPD1), rat anti-mouse PDL1 (B7-H1) antibody (αPDL1) and rat isotype control (anti-trinitrophenol) antibody (IgG2a): all purchased from the United States Bio X Cell Corporation.

[0122] 1. Binding of bispecific nanobodies to tumor cells and T cells

[0123] 1. In order to simulate the tumor microen...

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Abstract

The invention relates to a nanometer aptamer for multispecific antibody delivery as well as an application and construction method of the nanometer aptamer. The nanometer aptamer is formed by connecting a nanometer carrier with an anti-Fc segment antibody or an anti-Fc segment antibody fragment part through a chemical bond, wherein an Fab domain of the anti-Fc segment antibody or anti-Fc segment antibody fragment is capable of being non-covalently bound to the Fc domain of the delivered specific antibody; and the delivered specific antibody has the same species source as the anti-Fc fragment antibody or the Fc segment recognized by the anti-Fc segment antibody fragment. The nanometer aptamer disclosed by the invention can be quickly, efficiently and controllably combined with various typesof antibodies, so that'multivalence'and 'multispecificity' of the antibodies are realized. A constructed nanometer antibody delivery platform is creatively applied to preparation of immunotherapy drugs or treatment drugs for tumors or autoimmune diseases for the first time, and the immunotherapy effect can be obviously improved.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to a nano-adapter for multi-specific antibody delivery and its application and construction method. Background technique [0002] Malignant tumors are still a major public health problem that seriously threatens the health of residents. In recent years, tumor immunotherapy, especially immune checkpoint blockade therapy, has developed rapidly and is profoundly changing the treatment pattern of malignant tumors. Immune checkpoint blocking antibodies have become a new hotspot in the global biopharmaceutical field. Clinical results show that immune checkpoint antibody therapy can activate anti-tumor immune responses to varying degrees in some tumor patients and produce specific anti-tumor memory effects that last for several years. Although a variety of immune checkpoint blocking antibodies have been approved for the treatment of various types of tumors and indications, showing great...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/54A61K39/395A61P37/02A61P35/00
CPCA61K47/549A61K39/39533A61P37/02A61P35/00A61K2039/507
Inventor 沈松王均江澄涛许从飞杨显珠
Owner SOUTH CHINA UNIV OF TECH