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Immunotherapy curative effect prediction marker and prediction model construction and application

An immunotherapy and predictive model technology, applied in the field of immunotherapy, can solve the problem of little understanding of the impact of biomarker accuracy, and achieve the effect of wide applicability and improved accuracy

Pending Publication Date: 2022-04-15
XIANGYA HOSPITAL CENT SOUTH UNIV
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Problems solved by technology

[0003] However, these markers are mainly used for patient assessment before ICB treatment, and the impact of dynamic changes during treatment on the accuracy of these biomarkers is poorly understood

Method used

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  • Immunotherapy curative effect prediction marker and prediction model construction and application
  • Immunotherapy curative effect prediction marker and prediction model construction and application
  • Immunotherapy curative effect prediction marker and prediction model construction and application

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Such as figure 1 Shown:

[0024] Using bioinformatics analysis to systematically analyze the cancer genome atlas (The Cancer Genomics Atlas) contains 33 cancers, metastatic tumor data sets of more than 1000 samples, as well as 14 active and 20 independent ICB treatment data sets Pairwise correlations between the expression of suppressed immune checkpoints, as well as the abundance of various types of immune cells, suggest that these immune signatures are in homeostasis ( figure 1 A-B); where (A) samples were collected from primary tumors, metastatic tumors, and ICB-treated patients; (B) the relationship between activated and inhibited checkpoints and the relative abundance of immune cell populations. (C) Clinical impact of treating patients with ICB by non-invasive kinetic analysis of blood samples; (D) proof-of-concept evidence for kinetic analysis in plasma to predict response to immunotherapy;

[0025] Further comparing the changes of immune characteristics in TIME...

Embodiment 2

[0027] Such as Figure 1-2 shown

[0028] Clinically, in two independent anti-PD-1 monoclonal antibody lung cancer treatment cohorts, the expression of ILs in the plasma of patients after 2 cycles (4-6 weeks) after the start of treatment was detected, and a model for predicting the efficacy of immunotherapy was established ( figure 1 D. figure 2 A-E), and validate the model accuracy in different datasets ( figure 2 F-H). This method is non-invasive, low-cost and high-efficiency, and can evaluate the curative effect of ICB in the early stage of treatment, which is earlier than traditional detection methods based on imaging, and is a new paradigm for dynamically predicting the curative effect of immunotherapy.

[0029] Such as figure 2 A dynamic map of immune signatures predicting response to immunotherapy is shown. (A) Schematic of sample collection from lung cancer patients treated with anti-PD-1 alone or chemotherapy and anti-PD-1 combined. (B) Differences in IL expre...

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Abstract

According to the immunotherapy curative effect prediction marker disclosed by the invention, after a patient benefited from ICB treatment starts two cycles of immunotherapy (4-6 weeks), the reaction of the patient to the immunotherapy can be predicted by activating interleukin (ILs) in the plasma of the patient; the time is 6-12 weeks earlier than that of traditional computed tomography (CT), and the method is crucial to cancer patients receiving immunotherapy; the construction of the immunotherapy activation prediction marker and the prediction model is non-invasive dynamic analysis of blood detection before treatment and at the early stage of treatment, and has important significance in predicting the curative effect of immunotherapy; the technical scheme provided by the invention has guiding significance for predicting the long-term curative effect of a tumor immunotherapy patient. The dynamic prediction model improves the accuracy of immunotherapy curative effect prediction, and has wide clinical applicability.

Description

technical field [0001] The invention relates to the construction and application of markers for predicting curative effect of immunotherapy and predictive models, and relates to the technical field of immunotherapy. Background technique [0002] Tumor immunotherapy is a revolution in medicine. How to accurately predict the efficacy of immunotherapy is a challenge for immunotherapy. However, traditional methods such as detecting tumor mutation load and PD-L1 protein expression before treatment cannot effectively predict the efficacy of all patients; immune checkpoint blockade (Immune Checkpoint Blockade, ICB ) therapy has shown significant clinical benefits in different cancers, but the response rate of most patients is relatively low, which is closely related to the tumor immune microenvironment (TumorImmune Microenvironment, TIME). TIME includes a variety of immune cell populations with diversity and plasticity, as well as the expression of various activating and suppressi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68G01N33/574G16H50/50G16B5/00
Inventor 刘洪陈翔高骞叶幼琼
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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