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Preparation method of hydrogel tumor vaccine, hydrogel tumor vaccine prepared by preparation method and application of hydrogel tumor vaccine

A tumor vaccine and hydrogel technology, which is applied in the direction of anti-tumor drugs, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve the problems of long technical cycle, high cost, unfavorable long-term treatment of cancer patients, etc., and achieve the promotion of maturation , promote infiltration, and prolong the effect of immune memory effect

Active Publication Date: 2019-09-24
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

With the development of sequencing technology, tumor neoantigens provide a new idea for the design of personalized tumor vaccines. However, the technical cycle of tumor neoantigens is long and the cost is high, which is not conducive to the long-term treatment of advanced and highly malignant cancer patients.

Method used

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  • Preparation method of hydrogel tumor vaccine, hydrogel tumor vaccine prepared by preparation method and application of hydrogel tumor vaccine
  • Preparation method of hydrogel tumor vaccine, hydrogel tumor vaccine prepared by preparation method and application of hydrogel tumor vaccine
  • Preparation method of hydrogel tumor vaccine, hydrogel tumor vaccine prepared by preparation method and application of hydrogel tumor vaccine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1 The preparation of the hydrogel carrier of the present invention

[0037] Taking the (FMOC)FMOC-KRGDK polypeptide sequence as an example: a permeable hydrogel carrier was prepared by using a constant temperature water bath method, as a carrier for tumor cells, endowing the vaccine with stability and injectability.

[0038] Specific operation process:

[0039] Take 5 mg of (FMOC)FMOC-KRGDK polypeptide and 0.92 mg of anhydrous sodium carbonate, and dissolve them together in 0.5 mL of PBS buffer (pH 7.4), and place the resulting solution in a constant temperature water bath at 70 ° C until the formation of a hydrogel. Before the water bath (0 min), during (5 min after the start of the water bath), and after (50 min after the start of the water bath), an appropriate amount of hydrogel was taken to observe the formation process and microscopic morphology of the hydrogel with a transmission electron microscope, as shown in Fig. figure 1 shown. After the formati...

Embodiment 2

[0040] Example 2 Preparation of pretreated tumor cells of the present invention

[0041] Taking the mouse breast cancer 4T1 cell line as an example: the mouse breast cancer 4T1 cells were used as the cell model to prepare cell vectors; the photosensitive molecule indocyanine green (ICG) and the immunomodulator JQ 1 were used as model drugs and loaded into 4T1 cells.

[0042] Specific operation process:

[0043] Collect 4T1 tumor cells (1×10 7 ), placed in 1mL Foxp3 fixative solution and incubated for 30min, washed 3 times with PBS, then added 5mL methanol solution containing indocyanine green and JQ1, mixed evenly, stirred for 4h, in which the concentrations of indocyanine green and JQ1 were both 10μg / mL. After 2 hours, centrifuge at 2000 rpm for 3 minutes to remove free drug, and wash with PBS 3 times to obtain 4T1 cells loaded with indocyanine green and JQ1.

Embodiment 3

[0044] Example 3 Preparation of Hydrogel Tumor Vaccine of the Present Invention

[0045] The 4T1 cells loaded with indocyanine green and JQ1 obtained in Example 2 were mixed with the hydrogel carrier obtained in Example 1 to prepare a hydrogel tumor vaccine, and the hydrogel tumor vaccine was inoculated with 4T1 tumor-bearing Balb / After the c mice were inoculated with 4T1 tumor cells, the protective effect of the vaccine on the mice was observed.

[0046] Specific operation process:

[0047] Take 1 mL of the hydrogel carrier obtained in Example 1, slowly add 1×10 7 The 4T1 cells loaded with indocyanine green and JQ1 obtained in Example 2 are fully vortexed and mixed and then left to stand to obtain a hydrogel tumor vaccine. The specific process is as follows Figure 4 shown.

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Abstract

The invention discloses a preparation method of a hydrogel tumor vaccine, the hydrogel tumor vaccine prepared by the preparation method and application of the hydrogel tumor vaccine. The preparation method comprises the steps as follows: 1) tumor cell pretreatment: adding a hydrophobic drug to tumor cells serving as a carrier to obtain pretreated tumor cells; 2) preparation of a hydrogel carrier: dissolving polypeptides and inorganic alkali in a buffer solution, and after full dissolution, carrying out heating in a water bath at 30-90 DEG C for 5-50 min to prepare the hydrogel carrier; and 3) preparation of the hydrogel tumor vaccine: in a vortex state, slowly adding the hydrogel carrier prepared in the sep 2) to the pretreated tumor cells prepared in the step 1), performing uniform mixing, and leaving the mixture to stand to obtain the hydrogel tumor vaccine. The hydrogel tumor vaccine combines a tumor cell vaccine and the hydrophobic drug, and can inhibit immune evasion mechanisms while enhancing specific antigen presentation and efficiently inhibit tumor metastasis and recurrence.

Description

technical field [0001] The invention relates to the fields of biomedicine and tumor treatment, in particular to a preparation method of a personalized tumor vaccine based on tumor cells in a body, a tumor vaccine prepared by the preparation method, and an application thereof. Background technique [0002] Tumor recurrence and metastasis are the biggest challenges in cancer treatment. Traditional treatment methods such as surgery, chemotherapy and radiotherapy have limited efficacy for recurrent and metastatic tumors. In recent years, cancer immunotherapy has a remarkable effect on recurrent or metastatic tumors, and is receiving widespread attention. Among them, tumor vaccines play an important role in the treatment of preventing cancer recurrence and metastasis, but the efficacy of traditional tumor vaccines varies greatly among different patients. The main reason is that most of the currently studied tumor vaccines are aimed at a single antigen molecule of tumor cells or...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K9/06A61K45/06A61P35/00A61P35/04
CPCA61K39/0011A61K45/06A61K9/06A61K47/42A61P35/00A61P35/04A61K2039/5152A61K2039/57
Inventor 于海军李亚平王亭亭王当歌张汉武周蕾
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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