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An early screening device for immunotherapy acquired drug resistance and its application

An immunotherapy and acquired technology, applied in the direction of microbial determination/testing, sequence analysis, instruments, etc., can solve the problem of early screening methods for immature drug resistance, untimely detection of acquired drug resistance, untimely treatment of patients, etc. problem, achieve good sensitivity, easy adjustment, and avoid damage and pain

Active Publication Date: 2022-05-13
PEKING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the one hand, this method has a hysteresis, and it is usually found that the patient’s condition is already serious when acquired drug resistance occurs, resulting in a delay in the treatment of the patient; necessary medical expenses
Therefore, the untimely detection of acquired drug resistance by traditional technology will not only be detrimental to treatment, but also lead to economic losses for patients.
[0005] There is currently no proven method for early screening of acquired resistance to immunotherapy

Method used

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  • An early screening device for immunotherapy acquired drug resistance and its application
  • An early screening device for immunotherapy acquired drug resistance and its application
  • An early screening device for immunotherapy acquired drug resistance and its application

Examples

Experimental program
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Effect test

Embodiment 1

[0079] In this example, the data of tumor samples corresponding to 33 cancer patients (head and neck cancer, lung cancer, and breast cancer) who did not receive immunotherapy, did not respond after immunotherapy, and responded after immunotherapy were collected, and the single-cell sequencing data of T cells were analyzed. . Among them, immunotherapy is PD-1 antibody therapy or PD-L1 antibody therapy. The antigen specificity of each CD8 T cell clone analyzed has been verified by in vitro experiments or related computational analysis based on in vitro experiments.

[0080] The result is as figure 2 shown. It can be seen that all CD8 T cell clones are divided into cancer cell killing CD8 T cells that can recognize tumor antigens, and non-cancer cell killing CD8 T cells that recognize specific influenza virus antigens. The results showed that cancer cell-killing CD8 T cell clones from tumors that did not receive immunotherapy and did not respond after treatment highly express...

Embodiment 2

[0082] The expression of CXCL13 and CD8A of all CD4 T cell clones and CD8 T cell clones in the sample in Example 1 was analyzed. The result is as image 3As shown, the expression levels of CD8A and CXCL13 can effectively identify cancer cell-killing CD8 T cell clones. In this embodiment, 0.9 is directly used as the threshold value of CD8A expression level, and 0.15 is used as the threshold value of CXCL13 expression level. If the expression level of CD8A is greater than or equal to 0.9 and the expression level of CXCL13 is greater than or equal to 0.15, it is considered to be a cancer cell killing CD8 T cell clone. Using this method to screen T cell clones, the accuracy rate can reach 96.9%.

Embodiment 3

[0084] To all Exhaustion in embodiment 1 hi CXCL13 + CD8A + T cells and Exhaustion low CXCL13 + CD8A + Unsupervised clustering analysis of T cells found that these cancer-killing CD8 T cells can be divided into 4 subgroups (such as Figure 4 shown), including proliferative T cells (high expression of genes such as MKI67 and STMN1), exhausted T cells (high expression of genes such as HAVCR2, ENTPD1, ​​LAYN, PDCD1, TIGIT, LAG3 and CTLA4) and non-exhausted precursor T cells, Non-exhausted precursor T cells can be further divided into GZMK-positive precursor T cells and IL7R-positive precursor T cells (high expression of IL7R, TCF7, LEF1, CCR7, and SELL genes).

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Abstract

The present invention provides an early screening device for immunotherapy acquired drug resistance and its application. The early screening device for immunotherapy acquired drug resistance includes a sequencing module, a screening module, a cluster analysis module, a monitoring module and an analysis module. module. The present invention also provides an early screening method for immunotherapy acquired drug resistance for the purpose of non-disease diagnosis and / or treatment. The present invention monitors the change in the proportion of the peripheral blood cancer cell killing CD8 T cell clone in real time, and combines the change of the proportion of the non-exhausted precursor T cell in the cancer cell killing CD8 T cell clone in the biopsy sample to make a comprehensive judgment, and can Whether the sample has acquired acquired drug resistance to immunotherapy is screened very early, and the result is accurate and applicable, which provides a theoretical basis for related treatment and medication, and has important guiding significance.

Description

technical field [0001] The invention belongs to the technical field of immunotherapy, and in particular relates to an early screening device for immunotherapy acquired drug resistance and its application. Background technique [0002] Immune checkpoint blockade therapy represented by PD-1 antibody therapy has improved the treatment landscape of cancer. Some cancer patients respond to drugs after receiving immune checkpoint blockade therapy, and their condition gradually improves; however, 15% to 20% of patients begin to aggravate their condition within a period of time after the treatment takes effect, and the tumor becomes larger and new tumors appear. Tumor metastasizes and develops acquired resistance to treatment. [0003] At present, the hospital will evaluate the cancer patient three months after the first immunotherapy, and if there is no obvious disease progression or serious side effects, the immunotherapy will continue; if the cancer patient is found through imagi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886C12Q1/6881G16B30/00
CPCC12Q1/6886C12Q1/6881G16B30/00C12Q2600/158C12Q2600/106
Inventor 刘宝琳张园园张泽民
Owner PEKING UNIV
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