Method for assessing a prognosis and predicting the response of patients with malignant diseases to immunotherapy

A technology for immunotherapy and disease, applied in the field of implementing the method or the kit for the use, and molecular diagnosis, which can solve the problems that clinicians do not have, lack of prognosis and prediction methods, and inaccurately estimate the course of disease of individual patients, etc.

Active Publication Date: 2019-05-03
迪莫迪特里希
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these tests showed only moderate reliability
[0010] As previously mentioned, treatment options for patients with malignant disease are in many cases suboptimally selected because the course of an individual patient's disease can often only be estimated imprecisely, so clinicians do not have sufficient basis for individualized selection or adjustment when available treatment
Therefore, there is a lack of a reliable and economical prognostic and predictive method that is based on objectively measured parameters and that makes it possible to accurately estimate the course of the disease and reliably predict the response to therapy in patients with different malignancies

Method used

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  • Method for assessing a prognosis and predicting the response of patients with malignant diseases to immunotherapy
  • Method for assessing a prognosis and predicting the response of patients with malignant diseases to immunotherapy
  • Method for assessing a prognosis and predicting the response of patients with malignant diseases to immunotherapy

Examples

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Embodiment 1

[0135] Example 1: Determining the prognosis of patients after radical resection of prostate cancer based on the DNA methylation analysis of the immune regulatory gene PDCD1

[0136] According to a method embodiment of the present invention, determination of the prognosis of a patient may be performed in locally confined (localized, non-spread) prostate cancer, for example after radical prostatectomy and radical resection of tumors located in the prostate rear.

[0137] First, DNA is obtained from the tumor. For example, proteinase K can be used to lyse tumor tissue, followed by silica spin column extraction of DNA. For obtaining DNA from tumors, commercially available kits such as QIAamp DNA Mini Kit (Qiagen N.V., Helden, Germany) are commercially available. Subsequent bisulfite conversion of the extracted DNA deaminates essentially all cytosines to uracil, leaving methylated cytosines unchanged. Methylation analysis is then performed using, for example, the Infinium HumanM...

Embodiment 2

[0141] Example 2: Determining the prognosis of prostate cancer patients after radical resection based on DNA methylation analysis of the immune regulatory gene CD274

[0142] By implementing the method according to the present invention, it is also possible to determine the prognosis of patients with malignant diseases through DNA methylation analysis of CpG dinucleotides within the CD274 gene. For example, the prognosis of patients with locally restricted prostate cancer was obtained based on the methylation of the CD274 gene within the tumor after the patient underwent complete removal (radical resection) of the prostate and tumors located in the prostate.

[0143] In total, tumor samples from 417 patients with known prognosis were analyzed retrospectively. DNA methylation analysis was performed as described in Example 1. In order to calculate the relative methylation value of the CD274 gene locus based on the Infinium HumanMethylation450BeadChip raw data, five bead pairs c...

Embodiment 3

[0150] Example 3: Determining the prognosis of malignant melanoma patients based on DNA methylation analysis of the immune regulatory genes PDCD1, PDCD1LG2 and CD274

[0151] This example shows the determination of the prognosis of 470 patients with malignant melanoma according to the present invention. The results of the DNA methylation analysis were generated using the Infinium HumanMethylation 450 BeadChip as described in Example 1. To determine the relative methylation values ​​of the corresponding genes, the relative methylation values ​​were first determined as described in Example 1 for each selected bead of the Infinium HumanMethylation450BeadChip. The relative methylation values ​​of up to six bead pairs per gene were then averaged to obtain representative methylation values ​​for a specific gene. In order to carry out methylation analysis to CD274, use bead pair cg15837913 (SEQ ID NO:8), cg02823866 (SEQ ID NO:9), cg14305799 (SEQ ID NO:10), cg13474877 (SEQ ID NO:11) ...

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Abstract

The invention relates to, among others, a method for assessing a prognosis of a patient with a malignant disease and / or for predicting the response of a patient with a malignant disease to immunotherapy. For this purpose, a DNA methylation analysis is carried out on at least one immunoregulatory gene of cells of the malignant disease and / or T lymphocytes which interact with the cells of the malignant disease, said gene coding for an immune checkpoint selected from B7 proteins and the receptors thereof, MHC-peptide complex-binding co-receptors, the members of the tumor necrosis factor receptorsuperfamily TNFRSF9, CD40, TNFRSF4, TNFRSF18, and CD27, the members of the immunoglobulin superfamily TIGIT, BTLA, HAVCR2, BTNL2, and CD48, and the andenosine-binding adenosine 2A receptor.

Description

[0001] related application [0002] This patent application claims priority from German Patent Application No. DE 10 2016 005 947.8, the disclosure content of which is incorporated herein by reference. [0003] sequence listing [0004] This application includes as part of the specification an electronic sequence listing with 485 sequences in txt format according to WIPO ST.25 standard, the contents of which are incorporated herein by reference. technical field [0005] The present invention relates to molecular diagnostic methods in the field of oncology, with which the prognosis of patients with malignant diseases can be assessed, or the response of patients with malignant diseases to immunotherapy can be predicted. The present invention also relates to molecular diagnostic methods that allow individualized selection of suitable drugs for the immunotherapy of these patients. Accordingly, the present invention also relates to the use of these methods for prognostic determin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q2600/106C12Q2600/154C12Q2600/118C12Q1/6886
Inventor 迪莫·迪特里希
Owner 迪莫迪特里希
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