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Blood-based tumor mutation burden (bTMB) biomarker, and measuring method and uses thereof

A biomarker and sequencing technology, applied in the determination/test of microorganisms, biochemical equipment and methods, etc., can solve problems such as the inability to effectively predict the OS benefit of tumor patients receiving immunotherapy

Active Publication Date: 2020-01-03
CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to solve the defect that the existing bTMB calculation method cannot effectively predict the OS benefit of tumor patients receiving immunotherapy, the purpose of the present invention is to provide a new bTMB (LAF-bTMB) and its assay method. The LAF-bTMB biomarker of the present invention And the determination method can eliminate the interfering factors in the blood that affect the prediction performance of bTMB, accurately screen the population who can benefit from the OS and PFS from immunotherapy, effectively guide the immunotherapy, and meet the clinical needs of tumor patients

Method used

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  • Blood-based tumor mutation burden (bTMB) biomarker, and measuring method and uses thereof
  • Blood-based tumor mutation burden (bTMB) biomarker, and measuring method and uses thereof
  • Blood-based tumor mutation burden (bTMB) biomarker, and measuring method and uses thereof

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Experimental program
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Effect test

Embodiment 1

[0052] Immunotherapy versus chemotherapy in patients with non-small cell lung cancer, and within the immunotherapy group, the prognosis for OS and PFS benefit Measurement

[0053] Sources of bTMB detection data and patient clinicopathological data

[0054] Firstly, data from POPLAR (NCT01903993, N=211) and OAK (NCT02008227, N=642) studies were combined. The POPLAR study is a phase II randomized controlled trial comparing second / third-line atezolizumab with standard-of-care docetaxel chemotherapy in patients with advanced or metastatic non-small cell lung cancer who were not screened for PD-L1 expression. The OAK study was a phase III randomized controlled trial comparing atezolizumab versus docetaxel chemotherapy in patients with metastatic non-small cell lung cancer. bTMB detection data and patient clinicopathological parameters in both studies were white https: / / clinicalstudvdatarecluest.com / .

[0055] LAF-bTMB Calculation

[0056] The sum of the number of s...

Embodiment 2

[0072] LAF-bTMB guides immunotherapy for non-small cell lung cancer patients in China

[0073] Patient Recruitment

[0074] From August 1, 2016 to January 1, 2018, 64 patients with advanced non-cancerous patients receiving first / second / third-line immunotherapy (anti-PD-1 / PD-L1) were enrolled in Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College Hospital. patients with small cell lung cancer. This study was approved by the ethics committees of all participating institutions. All enrolled patients signed an informed consent form before the start of the study. The recruited patients are hereinafter referred to as the NCC cohort.

[0075] bTMB detection and LAF-bTMB calculation

[0076] The detection method of bTMB has been disclosed in the document JAMA Oncol.2019Feb 28.doi:10.1001 / jamaoncol.2018.7098. The panel used for the detection is NCC-GP150 covering 150 genes, which has also been disclosed in the document JAMAOncol.2019Feb 28...

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Abstract

The invention relates to a blood-based tumor mutation burden (bTMB) biomarker, and an measuring method and uses thereof. The bTMB biomarker is obtained from the following steps that cell-free DNA (cfDNA) is obtained from a blood sample of a subject, the number of somatic mutations on sequencing bases is measured, the number of somatic mutations of low allele abundance is taken as the bTMB biomarker and expressed as LAF-bTMB, wherein the low allele abundance means that the allele frequency is less than, for example, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%,9%, 8%, 7%, 6%, 5%, 4 %, 3%, 2%, 1%, for example, between 0.3% to 25%, preferably less than, for example, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, for example, between 0.5% to 13%, andparticularly preferably less than 6.5%, 6%, 5.5%, 5%, 4.5%, 4 %, 3.5%, 3%, 2.5%, and the LAF-bTMB is calculated according to the total number of mutations in a sample measuring area.

Description

technical field [0001] The present invention relates to the fields of biomarkers and gene detection, more specifically, to a blood tumor mutation burden (bTMB) biomarker measured by circulating tumor DNA, a measurement method and application thereof. Background technique [0002] Tumor immune checkpoint inhibitors (hereinafter referred to as immunotherapy) are currently the most popular immunotherapy in the field of tumors, which include specific antibodies against programmed death receptor-1 and its ligands (anti-PD-1 / PD-L1) And cytotoxic T lymphocyte-associated antigen 4 antibody (anti-CTLA-4), etc. These drugs inhibit the immune escape of tumor cells and mobilize the patient's own immune system to eliminate tumors. At present, immunotherapy has made breakthroughs in the treatment of various advanced solid tumors, especially it can effectively prolong the overall survival (OS) of patients, and the adverse reactions are controllable. However, in the population without mar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/106C12Q2600/156C12Q2600/118
Inventor 王洁王志杰段建春白桦赫捷高树庚蔡尚立王国强赵晶高婵赵征怡熊磊
Owner CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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