Glycoconjugate containing stn or f-stn and its preparation method and application in antitumor vaccine

A technology of glycoconjugates and vaccines, applied in the application field of anti-tumor vaccines, can solve the problems of poor reproducibility of KLH protein and limited clinical application

Active Publication Date: 2020-10-02
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the carrier protein KLH is a large heterogeneous protein complex with high glycosylation. The complexity of KLH protein leads to poor reproducibility of its preparation, which limits its clinical application.

Method used

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  • Glycoconjugate containing stn or f-stn and its preparation method and application in antitumor vaccine
  • Glycoconjugate containing stn or f-stn and its preparation method and application in antitumor vaccine
  • Glycoconjugate containing stn or f-stn and its preparation method and application in antitumor vaccine

Examples

Experimental program
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preparation example Construction

[0051] The invention provides a preparation method of the glycoconjugate, comprising the following steps:

[0052] (1) A compound as shown in formula III is oxidized by ozone to obtain a disaccharide containing an aldehyde group;

[0053]

[0054] (2) Coupling the aldehyde group-containing disaccharide obtained in step (1) with a carrier under the condition of reductive amination to obtain a glycoconjugate containing STn or F-STn.

[0055] In the present invention, the concentration of the ozone is preferably 30-50 mg / L, more preferably 40 mg / L. The temperature of the ozone oxidation is preferably -72°C. The time for the ozone oxidation is preferably 10-30 min, more preferably 15-25 min, most preferably 20 min. The ozonation oxidizes the alkene group in formula III to an aldehyde group.

[0056] In the present invention, the conditions of the reductive amination preferably add NaBH 3 CN; The disaccharide containing aldehyde group, carrier and NaBH 3 The mass ratio of C...

Embodiment 1

[0067] Preparation method for coupling hapten F-STn or STn with carrier protein to form conjugate

[0068] Dissolve the hapten (F-STn or STn, 10mg) in 2mL of anhydrous methanol, and pass through the air containing ozone at -72°C (ozone concentration is 50mg / L), when the system turns blue (about 10~ After 30 minutes), the ozone flow was stopped, and the system was still blue after 10 minutes. Nitrogen was introduced into the reaction system for about 10 minutes to remove excess ozone. 0.5 mL of dimethyl sulfide was added dropwise, and then the temperature of the reaction system was naturally raised to room temperature. After 2 hours, the solvent was removed from the reaction system under vacuum to obtain a hapten containing an aldehyde group. The latter was dissolved together with 5 mg of protein CRM197 in 10 mM phosphate buffer at pH 7.2, 7.5 mg of sodium cyanoborohydride was added, and reacted on a shaker at room temperature for 24 h. The desired glycoprotein conjugate STn-...

Embodiment 2

[0070] Glycoprotein conjugate STn-CRM197 or F-STn-CRM197 immunological activity test

[0071] 1. Test materials and sources

[0072] 1. Test compound: the glycoprotein conjugate prepared in Example 1 of the present invention.

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Abstract

The invention provides a glycoconjugate containing STn or F-STn and a preparation method thereof and application for an anti-tumor vaccine, and belongs to the technical field of glycoconjugates. The glycoconjugate containing STn or F-STn comprises STn or F-STn and a vector; STn or F-STn is coupled to the vector through a connecting bond; the connecting bond includes an amido bond or an oxime bondor a C-N bond; the vector includes protein or zwitter-ion polysaccharide or lipid or nucleic acid. The glycoconjugate is applied to preparing an anti-tumor or anti-cancer vaccine or preparing a medicine for improving cell and / or humoral immune response. The vaccine prepared from the glycoconjugate of F-STn can improve humoral immunity and cellular immunologic response, the generated antibody can effectively recognize STn positive tumor cells, and the STn positive tumor cells can be cracked in an ADCC and CDC way.

Description

technical field [0001] The invention belongs to the technical field of glycoconjugates, and in particular relates to glycoconjugates containing STn or F-STn, a preparation method thereof and an application in antitumor vaccines. Background technique [0002] In recent years, carbohydrate antigen-based anti-tumor vaccines have become a research hotspot (Keding, S. Carbohydratevaccines. Chem. Eng. News. 2004, 82, 31-35.). Among them, the antigen STn is a disaccharide structure containing sialic acid, which is mostly expressed in human lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, breast cancer, colorectal cancer, etc., but rarely expressed in normal tissues (Holmberg, L. ExpertRev.Vaccines 2004,3,655-663.), thus becoming an important target for tumor immunotherapy. [0003] Biomira combined the natural STn antigen with the carrier keyhole limpet hemocyanin (KLH) to construct a vaccine STn-KLH for preventing colorectal cancer and breast cancer metastasis H...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/00A61K39/385A61K47/64A61K47/61A61K47/54A61P35/00
CPCA61K39/001169A61K39/385A61K47/544A61K47/549A61K47/61A61K47/6415A61K47/643A61K2039/575A61K2039/60A61K2039/6025A61K2039/6037A61K2039/6081A61K2039/6087A61K2039/62A61P35/00
Inventor 叶新山宋成程郑秀静李勤
Owner PEKING UNIV
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