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GalNAc/CpG liposome vaccine with anti-tumor activity as well as preparation method and application of GalNAc/CpG liposome vaccine

A technology of anti-tumor activity and liposomes, which is applied in the direction of anti-tumor drugs, liposome delivery, and medical preparations of non-active ingredients, etc. It can solve the complex synthesis steps of vaccine vectors, clinical application limitations, and difficult qualitative vaccine components and other problems, to achieve good particle size and stability, narrow distribution, and simple synthesis steps

Active Publication Date: 2021-10-15
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the protein or polypeptide carrier itself can cause strong immunity and thus suppress the immune response to the sugar antigen. At the same time, the synthesis steps of the vaccine carrier are complicated and the problems of vaccine components that are difficult to characterize need to be solved urgently, so there is still a big gap in its clinical application. limit

Method used

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  • GalNAc/CpG liposome vaccine with anti-tumor activity as well as preparation method and application of GalNAc/CpG liposome vaccine
  • GalNAc/CpG liposome vaccine with anti-tumor activity as well as preparation method and application of GalNAc/CpG liposome vaccine
  • GalNAc/CpG liposome vaccine with anti-tumor activity as well as preparation method and application of GalNAc/CpG liposome vaccine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] 1. Chol-C 2 -N 3 Synthesis

[0046] 2-Azidoethanol (0.67g, 7.8mmol) and triethylamine (0.73mL, 5.1mmol) were dissolved in dichloromethane (40mL), and cholesterol formyl chloride Chol-COCl ( 4.1 g, 9.2 mmol), then the solution was returned to room temperature, and the reaction was stirred overnight. After the reaction, it was washed with saturated sodium bicarbonate solution and dried over anhydrous magnesium sulfate. The excess solvent was removed by distillation under reduced pressure, separated by silica gel column chromatography, the mobile phase was petroleum ether / ethyl acetate (20 / 1), Rf=0.5, and the obtained product was used 1 H NMR and 13 The results of C NMR characterization are as follows figure 1 , figure 2 Shown: 1 H NMR (400MHz, CDCl 3 ):δ5.44-5.31(m,1H),4.56-4.43(m,1H),4.31-4.22(m,1H),3.58-3.46(m,1H),3.25(s,2H),2.45-2.22 (m, 2H), 2.06-1.76 (m, 5H), 1.73-0.79 (m, 39H). 13 C NMR (100MHz, CDCl 3 ):δ155.58 140.04123.08 78.39 77.36 77.04 76.72 74.29...

Embodiment 2

[0062] 1. Antigen presentation function of mouse bone marrow-derived dendritic cells BMDCs detected by flow cytometry

[0063] experiment procedure:

[0064] The femur and tibia of BALB / c mice were surgically separated, and both ends of the bone were cut off. The bone marrow cavity was repeatedly flushed with PBS drawn from a 1mL syringe, and the bone marrow tissue was blown away. Red blood cells were removed with ACK lysate to obtain a bone marrow single cell suspension. Adjust the cell density to 1 x 10 6 / mL, cells were cultured with RPMI 1640 complete medium, in which IL-4 (10ng / mL) and GM-CSF (20ng / mL) were added to stimulate the differentiation of bone marrow-derived dendritic cells BMDCs. Fresh media and cytokines were replaced every two and a half volumes. On day 7, the suspended and loosely attached cells were collected as BMDCs. Glycoliposome vaccine (10 μg / mL) stimulated BMDCs for 48 hours, and the cells were collected. With anti-CD40, anti-CD80, anti-CD86 and a...

Embodiment 3

[0080] 1. ELISA identification of the binding ability of glycolipidosome vaccine and Tn antibody

[0081] experiment procedure:

[0082] Glycoliposome vaccine (10 μg / mL) was co-incubated with anti-Tn antibody (Isotype IgM, 5 μg / mL) for 2 hours at 37° C., and the supernatant was collected after centrifugation at 5000 rpm. Using the ELISA method, coat the 96-well plate with Tn antigen overnight, use biotin-labeled anti-IgM antibody as the detection antibody to detect the concentration of anti-Tn antibody, and use the control group 5 μg / mL as the standard to calculate the anti-Tn antibody in the sample Concentration, concrete experimental procedure is as described in embodiment 2 (2). Experimental results such as Figure 11 shown.

[0083] It can be seen from the results in the figure that the GalNAc / CpG liposome vaccine can specifically bind to the Tn antibody, showing good antigenicity.

[0084] 2. ELISA detection of serum antibody titer of immunized mice

[0085] experime...

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Abstract

The invention discloses a GalNAc / CpG liposome vaccine with anti-tumor activity as well as a preparation method and application of the GalNAc / CpG liposome vaccine. The vaccine comprises a Tn antigen GalNAc, cholesterol and a nucleic acid adjuvant CpG ODN. According to the invention, a Chol-GalNAc compound is constructed through a Click reaction, the components of the vaccine can be clearly represented, and the vaccine has the characteristic of biodegradability. The liposome vaccine entrapped with the adjuvant CpG ODN is constructed through a film-ultrasonic method, the purpose of antitumor activity of body fluid and cellular immunity can be achieved, and the liposome vaccine plays a role as a main active component in preparation of drugs for resisting breast cancer and the like. Experiments prove that the GalNAc / CpG liposome vaccine has a good particle size, can well induce maturation of bone marrow derived BMDCs and spleen B cells of mice and induce the mice to generate specific antibodies, and can effectively activate cellular immunity of the mice to realize an anti-tumor effect.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and in particular relates to a glycolipidosome vaccine with antitumor activity, more specifically, the invention relates to a GalNAc / CpG liposome vaccine with antitumor activity, a preparation method and application thereof. Background technique [0002] Cancer vaccine is a promising strategy in the field of tumor immunotherapy by using the activation function of tumor-associated antigens and immune adjuvants to stimulate the body to generate a specific immune response against tumors, and then effectively kill tumors. Tumor associated carbohydrate antigens (TACAs) come from the glycocalyx structure on the surface of tumor cells. It is due to the restriction of the functions of glycosyltransferases and glycosidases in the process of cell canceration, resulting in glycoproteins and glycolipids. The mutated sugar molecule formed by the change of the sugar group in the glycoconjugate, incl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/385A61K39/39A61K39/00A61K9/127A61K47/54A61P35/00
CPCA61K39/385A61K39/0011A61K39/39A61K9/1277A61K47/554A61P35/00A61K2039/55561A61K2039/585
Inventor 陈国颂姚琳通张宇飞吴利斌王茹瑾
Owner FUDAN UNIV
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