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A predictive molecule for judging the curative effect of targeted monoclonal antibody therapy on tumor

A monoclonal antibody and targeting technology, applied in the biological field, can solve limitations and other problems, and achieve the effect of improving the quality of life and improving the curative effect

Active Publication Date: 2019-02-19
INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Research on the molecule is currently limited to inflammatory conditions such as pancreatitis

Method used

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  • A predictive molecule for judging the curative effect of targeted monoclonal antibody therapy on tumor
  • A predictive molecule for judging the curative effect of targeted monoclonal antibody therapy on tumor
  • A predictive molecule for judging the curative effect of targeted monoclonal antibody therapy on tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1, PRSS1 as a marker for judging whether the cells to be tested are resistant to cetuximab

[0051] 1. Identification of the molecule PRSS1 related to drug resistance

[0052] Through a large amount of literature research, a gene expression profile database (Affymetrix133A Microarrays) about 798 cell lines was found. The database is available from the Sanger Cell Line Project at http: / / www.broadinstitute.org / cgi-bin / cancer / datasets.cgi. After a large number of literature searches, it was found that among the 798 cell lines in this database, 19 cell lines (EGI-1, HCC70, COLO-205, HCT116, HT-29, LS1034, LS174T, RKO, SW620, PC-3 , KATOIII, MKN45, AGS, SAS, HuCCT1, A549, SW403, HCT15, TE-1) are cetuximab-resistant cell lines reported in the literature, 30 cell lines (MDA-MB-468, LoVo, SW48, HuH-7, SW1573, TE-5, KYSE-150, 22RV1, DU-145, MKN1, MKN28, NCI-N87, Ca9-22, CAL-33, HSC-2, HSC-3, FaDu, CAL- 39. U251, Ca-Ski, DoTc2-4510, ME-180, OMC-1, A498, ACHN, CAKI-1, S...

Embodiment 2

[0060] Example 2, PRSS1 improves the drug resistance of colon cancer cells to cetuximab

[0061] 1. Obtaining colon cancer cells overexpressing PRSS1 and colon cancer cells that interfere with PRSS1 expression

[0062] 1. Obtainment of colon cancer cells overexpressing PRSS1 full-length peptide and mature peptide

[0063] 1) Recombinant vectors and transfected cells overexpressing PRSS1

[0064] pMSCV-puro-PRSS1 is obtained by inserting the coding gene (sequence 1) of the full-length peptide of PRSS1 into the BglⅡ and SalⅠ restriction sites of pMSCV-puro (CLONTECH Company, catalog number PT3303-5, catalog #K1062-1) Carrier.

[0065] pMSCV-puro-PRSS1' is a vector obtained by inserting the coding gene of PRSS1 mature peptide (sequence 3) into the BglII and SalI restriction sites of pMSCV-puro.

[0066] pMSCV-puro-PRSS1, pMSCV-puro-PRSS1', and pMSCV-puro were transfected with LoVo (purchased from ATCC, USA, BNCC337953), respectively, to obtain colon cancer cells transfected wi...

Embodiment 3

[0116] Example 3, PRSS1 degrades the remaining monoclonal antibodies

[0117] To analyze whether PRSS can degrade other commercial monoclonal antibodies such as bevacizumab and trastuzumab.

[0118] Method is basically the same as 3 of 3 of Example 2, only cetuximab is replaced by bevacizumab (the name of the company is Roche Pharma (Schweiz) Ltd. The domestic contact is Shanghai Roche Pharmaceutical Co., Ltd., and the import registration standard: JS20110006) or trastuzumab (the name of the company is Roche Pharma (Schweiz) Ltd, the domestic contact is Shanghai Roche Pharmaceutical Co., Ltd., import registration standards: JS20110007 and JS20110008), and the colon cancer cells are HT-29.

[0119] The result is as Figure 10 As shown, PRSS1 in the cell supernatant was found to degrade bevacizumab and trastuzumab in addition to cetuximab.

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Abstract

The invention discloses a predication molecule for judging the tumor treatment effect of a targeting monoclonal antibody. The invention provides an application of a substance for detecting the PRSS1 expression level in the preparation of monoclonal antibody drug-resistant products for detecting whether tumor cells recognize a targeting EGFR or not, or an application of the substance for detecting the PRSS1 expression level in the preparation of monoclonal antibody drug-resistant products for detecting whether tumor patients recognize the targeting EGFR or not. Experiments prove that the PRSS1 can be used as a treatment effect detection molecule for assisting clinic medication, that is, the monoclonal antibody treatment effect of a patient is predicated through monitoring the expression level of the PRSS1 in the patient, and an effectively treatment scheme is timely replaced in order to enhance the patient treatment effect and improve the living quality of the patient.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a predictive molecule for judging the curative effect of a targeted monoclonal antibody in treating tumors. Background technique [0002] Colorectal cancer (CRC) is a common malignant tumor in the world. Its pathogenesis is related to genetic factors and environmental factors. The molecular mechanisms of its pathogenesis mainly include: increased genetic instability, methylation phenotype and K-ras, Mutations in genes such as B-raf. 40%-50% of patients with colorectal cancer have distant metastases at the time of diagnosis, and even if patients undergo radical surgical resection, more than 50% of patients will eventually develop recurrent metastases, so metastatic colorectal cancer (mCRC) Medication is especially important. Although chemotherapy drugs for CRC such as Irinotecan, Oxaliplatin, and Fluorouracil can improve the curative effect of mCRC, the median survival time of patie...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N33/577G01N33/574G01N33/573A61K45/00A61P35/00
CPCA61K45/00G01N33/56966G01N33/573G01N33/57446G01N33/577G01N2333/95
Inventor 王友亮谭招丽高丽华邵勇胡显文
Owner INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE