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Fusobacterium nucleatum as marker to predict curative effect of PD-L1 antibody therapy of colorectal cancer and application of maker

A technology of Fusobacterium nucleatum and PD-L1, applied in the field of biomedicine, can solve the problems of unclear, less than 30% effective rate, unsatisfactory immunotherapy effect, etc., to achieve good therapeutic effect and prolong survival period.

Active Publication Date: 2019-06-21
SHANGHAI TENTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effect of PD-1 / PD-L1 immunotherapy for colorectal cancer is not satisfactory, and the overall effective rate is less than 30%.
A large part of the reason is that it is not clear what type of colorectal cancer patients are effective for immunotherapy

Method used

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  • Fusobacterium nucleatum as marker to predict curative effect of PD-L1 antibody therapy of colorectal cancer and application of maker
  • Fusobacterium nucleatum as marker to predict curative effect of PD-L1 antibody therapy of colorectal cancer and application of maker
  • Fusobacterium nucleatum as marker to predict curative effect of PD-L1 antibody therapy of colorectal cancer and application of maker

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] This embodiment is a method and steps for detecting whether a colorectal cancer patient carries Fusobacterium nucleatum, including:

[0041] (1) Fusobacterium nucleatum DNA was extracted from the feces of patients with colorectal cancer;

[0042] The stool genomic DNA extraction kit (product number DP328) produced by Tiangen Biochemical Technology (Beijing) Co., Ltd. was used to extract DNA from the stool of colorectal cancer patients. The specific steps are as follows:

[0043] 1. Weigh 180-220mg of stool sample into a 2ml centrifuge tube and place the tube on ice.

[0044] 2. Add 500 μl Buffer SA, 100 μl Buffer SC, 15 μl Proteinase K, and 0.25 g of grinding beads to the sample, shake intermittently for 1 min until the sample is fully mixed.

[0045] 3. Incubate at 70°C for 15 minutes, shake 2-3 times during incubation.

[0046] 4. Vortex for 15 sec, centrifuge at 12,000 rpm (~13,400×g) for 3 min, transfer the supernatant to a new centrifuge tube, add 10 μl of RNase ...

Embodiment 2

[0111] This example verifies the relationship between Fusobacterium nucleatum and the immunotherapeutic effect of colorectal cancer PD-L1 antibody, and the experimental steps are as follows:

[0112] Use the mouse colon cancer cell line CT26.WT to form tumors subcutaneously in BalB / C mice, inject Fusobacterium nucleatum into the tumor at multiple points, and then inject anti-mouse PD-L1 antibody intraperitoneally, and observe the changes in tumor size. After the tumor tissue of mice with Fusobacterium nucleatum was treated with PD-L1 antibody, the tumor was significantly inhibited, while the tumor tissue without Fusobacterium nucleatum was not sensitive to PD-L1 antibody treatment. The results were as follows: figure 1 As shown, this indicates that Fusobacterium nucleatum enhances the immune efficacy of PD-L1 antibody in colorectal cancer.

Embodiment 3

[0114] This example verifies the effect of transplanting Fusobacterium nucleatum on the curative effect of PD-L1 immunotherapy-insensitive colorectal cancer, and the experimental steps are as follows:

[0115] After subcutaneous tumor formation of CT26.WT cells, PD-L1 antibody immunotherapy, compared with the untreated group, the tumor volume did not shrink significantly, indicating that CT26.WT is not sensitive to PD-L1 antibody immunotherapy, and then transplanted in tumors with Fusobacterium nucleatum, it was found that the tumor volume after PD-L1 antibody immunotherapy after transplantation of Fusobacterium nucleatum was significantly reduced, and the results were as follows figure 2 As shown, this illustrates that transplantation of Fusobacterium nucleatum enhances the efficacy of colorectal cancer that is insensitive to PD-L1 immunotherapy.

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Abstract

The invention relates to a preparation containing Fusobacterium nucleatum and PD-L1 antibody and used for immunotherapy of colorectal cancer, application of the preparation, a Fusobacterium nucleatummarker to predict curative effect of PD-L1 antibody therapy of colorectal cancer, and application of the marker. The influence of Fusobacterium nucleatum upon PD-L1 antibody immunotherapy of colorectal cancer is studied deeply herein, and it is discovered that PD-L1 monoclonal antibody therapy is more effective to colorectal cancer in the presence of Fusobacterium nucleatum, while PD-L1 monoclonalantibody therapy helps evidently extend the lifetime of a mouse with colorectal cancer in the presence of Fusobacterium nucleatum; by discussing the mechanism of Fusobacterium nucleatum, it is discovered that Fusobacterium nucleatum can provide transcriptional control for the expression of PD-L1; after PD-L1 antibody therapy is carried out for colorectal cancer tissues in the presence of Fusobacterium nucleatum, the proportion of CD8 positive T cells is increased; all these above are good for the effect of PD-L1 antibody therapy. It is indicated that the presence or absence of Fusobacterium nucleatum is suitable for acting as a potential marker to judge the curative effect of PD-L1 monoclonal antibody therapy for the patient with colorectal cancer; Fusobacterium nucleatum and PD-L1 monoclonal antibody can form an immunotherapy preparation for patients with colorectal cancer.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to Fusobacterium nucleatum as a marker for predicting curative effect of colorectal cancer PD-L1 antibody treatment and its application in colorectal cancer immunotherapy. Background technique [0002] Colorectal cancer is one of the common malignant tumors. With the development of immunotherapy, especially the "immune checkpoint" PD-1, PD-L1 and CTLA-4 monoclonal antibody drugs can effectively treat a variety of tumors. However, the effect of PD-1 / PD-L1 immunotherapy for colorectal cancer is not satisfactory, and the overall effective rate is less than 30%. A large part of the reason is that it is not clear what type of colorectal cancer patients are effective for immunotherapy. Therefore, further exploring the factors that affect the effect of immunotherapy in patients with rectal cancer is a key link in the precise treatment of patients with colorectal cancer. ...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P35/00A61P1/00A61B5/00C12Q1/6886G01N21/64G01N33/574A61K35/741
Inventor 高耀辉蔚青秦环龙
Owner SHANGHAI TENTH PEOPLES HOSPITAL
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