Application of p.P476S mutation of RBPJL gene as PD-1 antibody medication guiding marker

A technology of p.p476s and PD-1, which is applied in the determination/testing of microorganisms, biochemical equipment and methods, etc., can solve the problems of lack of treatment response and treatment resistance mechanism, achieve good application prospects and value, and improve treatment effect Effect

Active Publication Date: 2020-01-14
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Key predictors of treatment response and mechanisms of treatment resistance in patients with esophageal squamous cell carcinoma (ESCC) are lacking

Method used

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  • Application of p.P476S mutation of RBPJL gene as PD-1 antibody medication guiding marker
  • Application of p.P476S mutation of RBPJL gene as PD-1 antibody medication guiding marker
  • Application of p.P476S mutation of RBPJL gene as PD-1 antibody medication guiding marker

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment 1 clinical patient's toripalimab treatment situation

[0026] 1. Patient and Treatment

[0027] The patient was initially diagnosed as stage IV moderately differentiated esophageal cancer in the middle and lower part of the esophagus. On March 11, 2016 and April 06, 2016, platinum and paclitaxel chemotherapy regimens were used for 2 courses, and the curative effect was evaluated as PD (tumor progression). From May 7, 2016 to August 8, 2016, 7 courses of irinotecan chemotherapy were given as second-line chemotherapy, among which the curative effect was evaluated as SD after 3 courses of treatment, and PD (tumor progression) after 7 courses of treatment. Afterwards, the patient underwent a Phase I clinical trial (NCT02857166) of 6 cycles of toripalimab treatment (1mg / kg, q2w) in the Cancer Prevention and Control Center of Sun Yat-sen University.

[0028] The flow chart of the patient's PD1 treatment process is shown in figure 1 a.

[0029] 2. CT scan

[003...

Embodiment 2

[0051] Example 2 Screening of Liver Metastases Specific Mutation Genes

[0052] 1. Exome sequencing of primary and metastatic tissues of clinical patients

[0053] 1. Experimental method

[0054] To explore the genomic signatures of resistance to toripalimab in liver metastatic tissues from patients, DNA was extracted from primary and metastatic tissues after treatment and whole-exome sequencing was performed.

[0055] Total DNA was extracted from post-treatment plasma and primary and metastatic tumor biopsies, and then whole-exome sequencing was performed using Illumina Hiseq 2000. In the process of data processing, BWA-MEM. technology is used to compare and calibrate the human genome (HG19) data in UCSC at the same time, so as to identify high-quality genetic data. picard (v1.84; http: / / broadistitute.github.io / picard / ) was used to label and classify duplicate reads of data during PCR, followed by the genome analysis toolkit (gatk4, http: / / www .broadistitute.org / gatk) for ...

Embodiment 3

[0112] Example 3 RBPJL mutation affects T cell immune regulation ability

[0113] 1. Experimental method

[0114] Further studies were performed to detect the effects of different gene treatment groups of CMs on the differentiation of CD4+T cells. The specific experimental steps are as follows:

[0115] (1) After separating PBMCs by Ficoll-Paque Plus gradient centrifugation, CD3 magnetic beads were used to further purify T cells from PBMCs by positive selection and culture them in serum-free ImmunoCult-XF T Cell ExpMedium, and add CD3 / CD28 and IL- 2 stimulate the activation of T cells;

[0116] (2) Add the conditioned medium overexpressing each gene to the T cells and culture for 2 days; after the cell treatment, gently aspirate the medium, wash twice with pre-cooled PBS, and collect the cells;

[0117] (3) 1000rpm, centrifuge at room temperature for 5min, wash 3 times with preheated PBS, add diluted flow cytometry antibodies (CD4-PE, T-bet-PerCP / Cyanine5.5 and GATA-3-Alexa...

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Abstract

The invention discloses an application of p.P476S mutation of a RBPJL gene as a PD-1 antibody medication guiding marker. Through infiltration research of a very special answer mode after a patient suffering from trachea squamous cell carcinoma accepts PD-1 antibody treatment, the inventor finds that a p.P476S mutant site of the RBPJL gene can influence the treatment effects on liver metastasis ofthe patient suffering from squamous cell carcinoma, so that when the p.P476S mutant site of the RBPJL gene is used as a marker for guiding the PD-1 antibody treatment, a PD-1 antibody treatment schemeof the patient suffering from trachea squamous cell carcinoma generating liver metastasis can be effectively guided, and the treatment effect of the patient can be substantially promoted. The p.P476Smutation disclosed by the invention has good application prospect and value.

Description

technical field [0001] The present invention relates to the technical field of cancer treatment, and more specifically, relates to the application of p.P476S mutation of RBPJL gene as a guide marker for PD-1 antibody medication. Background technique [0002] Traditional therapies for esophageal cancer, including surgery, radiotherapy, and chemotherapy, have improved the prognosis of patients to a certain extent. At present, the treatment of tumors has entered a new era of immunotherapy. Among them, PD-1 therapy has been proven to significantly prolong the survival of patients in a variety of tumors, and the expression of PD-L1 in esophageal squamous cell carcinoma is closely related to the overall survival of patients, suggesting that targeting PD-1 / PD-L1 therapy may be both It has a good therapeutic effect. The activation and typing of T cells in the tumor microenvironment are closely related to the occurrence, development and prognosis of tumors. [0003] However, altho...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/106C12Q2600/156
Inventor 缪蕾
Owner SUN YAT SEN UNIV CANCER CENT
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