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Kinase activity signatures for predicting response of non-small cell lung cancer patients to PD-1 or PD-L1 immune checkpoint inhibitors

A non-small cell lung cancer, PD-L1 technology, applied in the direction of microbial determination/testing, measuring devices, instruments, etc., can solve the problems of patients' discomfort

Pending Publication Date: 2022-05-27
帕姆基因有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018] Furthermore, NSCLC biomarker assays, which are accurate early indicators of treatment response, often require lung biopsy, which is considered very unpleasant for patients

Method used

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  • Kinase activity signatures for predicting response of non-small cell lung cancer patients to PD-1 or PD-L1 immune checkpoint inhibitors
  • Kinase activity signatures for predicting response of non-small cell lung cancer patients to PD-1 or PD-L1 immune checkpoint inhibitors
  • Kinase activity signatures for predicting response of non-small cell lung cancer patients to PD-1 or PD-L1 immune checkpoint inhibitors

Examples

Experimental program
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Embodiment 1

[0367] Example 1. NSCLC patients with short-term progression and advanced (or no) progression on treatment with nivolumab or pembrolizumab can be differentiated based on kinase activity profiles (peptide microarrays).

[0368] PBMCs were isolated from 56 NSCLC patients (including two subgroups) shortly before treatment with an immune checkpoint inhibitor (ICI). All patients received anti-PD1 monotherapy with nivolumab or pembrolizumab and had not received any prior line of immunotherapy. PBMCs were lysed in MPER buffer in the presence of protease and phosphatase inhibitors, and 2 μg total protein was profiled for protein tyrosine kinase (PTK) activity using a dynamic peptide microarray (PamChip). The microarray contained 144 different peptides that are substrates for protein tyrosine kinases. The resulting phosphorylation profiles or kinase activity profiles were processed in R, including a normalization step (variance stabilization normalization, VSN) and correction for syst...

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Abstract

The present invention relates to a method for determining or predicting the response of a patient diagnosed with non-small cell lung cancer to a PD-1 or PD-L1 immune checkpoint inhibitor. The present invention also aims to provide methods and devices for predicting the response of a patient diagnosed with non-small cell lung cancer to a PD-1 or PD-L1 immune checkpoint inhibitor. More specifically, the present invention provides methods of measuring kinase activity and profile and inhibition of drugs thereto in a blood sample of said patient.

Description

[0001] Field of Invention [0002] The present invention relates to methods and devices for determining or predicting the response to a particular drug in a patient diagnosed with non-small cell lung cancer. More specifically, the present invention provides methods of measuring kinase activity in a blood sample of said patient. [0003] Background of the Invention [0004] Lung cancer is currently considered one of the most important causes of death, especially among adults aged 50 to 69. Long-term exposure to smoking is responsible for 90% of lung cancer cases. Among male smokers, the lifetime risk of developing lung cancer is about 17%; among female smokers, the risk is about 11%. For non-smokers, the risk of developing lung cancer is about 1 percent. The main causes of lung cancer in non-smokers are genetic factors, radon gas, asbestos, air pollution and passive smoking. There are two main types of lung cancer: non-small cell lung cancer (NSCLC) (about 80% of cases) and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/48G01N33/574
CPCC12Q1/485G01N33/57423
Inventor R.德维杰恩D.M.A.范登赫维尔
Owner 帕姆基因有限公司