Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of PD1 molecule inhibitor in T lymphocytic leukemia treatment

An inhibitor, PD-1 technology, applied in the biological field, can solve problems such as exacerbation and drug-resistant diseases

Inactive Publication Date: 2019-03-08
PERSONGEN BIOMEDICINESUZHOUCO
View PDF0 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But now there are reports that during PD-1 / PDL1 treatment, drug resistance or even disease exacerbation will appear in some patients, such as lung adenocarcinoma, head and neck squamous cell carcinoma, adult T-cell leukemia-lymphoma

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of PD1 molecule inhibitor in T lymphocytic leukemia treatment
  • Application of PD1 molecule inhibitor in T lymphocytic leukemia treatment
  • Application of PD1 molecule inhibitor in T lymphocytic leukemia treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Construction and characterization of a T-ALL xenograft model from a leukemia patient

[0081] Because primary T-ALL cells cannot grow in vitro, in order to expand T-ALL cells for subsequent experiments, a leukemia xenograft model was constructed on B-B-NDG mice. After injecting patient-derived T-ALL cells into the tail vein (5×10 6 cells, 6 mice), harvested mouse spleen cells ( figure 1 A). In order to verify that the spleen cells obtained from the mice are T-ALL cells, combined with the immunophenotype of the patient's primary T-ALL described above, cell surface marker staining and intracellular staining were performed by flow cytometry. Such as figure 1 As shown in B, the cells are negative for human CD33, CD19, and CD56, which excludes the possibility that the tumor cells are derived from myeloid cells, B cells, and NK cells. The cells express more than 90% of the surface markers human CD5 and CD7. Human cCD3 was also highly expressed, so it was determined that t...

Embodiment 2

[0083] Differences in the expression of immune checkpoints on T-ALL cells and healthy human T cells

[0084] Flow cytometry analysis was performed on T-ALL cells and peripheral blood T cells from several healthy people to detect the expression differences of various immune checkpoints. Depend on figure 2 A shows that, compared with healthy human CD3+ T cells, the expressions of PD-1, CD28, and CD200 on T-ALL cells are significantly up-regulated, while the expression of BTLA is significantly down-regulated, the expression of ICOS is slightly increased, and the expression of TIGIT is slightly reduced. When the expression of these immune checkpoints was analyzed by MFI, the results were also consistent ( figure 2 B).

Embodiment 3

[0086] Differences in the mRNA expression of ICOS, PD-1, BTLA, and CD200 on T-ALL cells and healthy human T cells

[0087] The above results indicated that ICOS, PD-1, BTLA, and CD200 were abnormally expressed on T-ALL cells in this case. Next, QPCR and RT-PCR were used to further verify their expression at the mRNA level. Such as image 3 As shown in A, compared with healthy people, the mRNA expression levels of ICOS and PD-1 on T-ALL cells are higher, and the difference is statistically significant. The expression of CD200 at the mRNA level is greatly increased, while BTLA is Expression at the mRNA level is almost absent. At the same time, a 293T cell line with stable expression of PD-1 was constructed as a positive control, and the transcripts of PD-1 on T-ALL and normal human PBMC were detected by RT-PCR ( image 3 B). Therefore, ICOS, PD-1, and CD200 are expressed on patient-derived T-ALL cells.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides application of a PD1 molecule inhibitor in T lymphocytic leukemia treatment. Concretely, the invention provides application of the PD1 molecule inhibitor, and the PD1 molecule inhibitor is used for preparing a medicine composition for inhibiting T-ALL cell differentiation and proliferation, and / or treating acute T lymphoblastic leukemia. The invention indicates that anti-PD-1 antibody therapy inhibits proliferation of T-ALL cells in spleens, and provides a certain experimental basis for the anti-PD-1 antibody clinically treating T-ALL.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to the application of PD1 molecular inhibitors in the treatment of T lymphocytic leukemia. Background technique [0002] Acute T-lymphoblastic leukemia (T-cell acute lymphoblastic leukemia, T-ALL) is a highly aggressive blood cancer, which is formed by the disordered proliferation of T cell progenitor cells. It accounts for about 15% of cases in children and 25% in adults. The current chemotherapy regimen for T-ALL is not ideal, and the remission rate can reach 85% in children's cases, while the remission rate in adult cases does not exceed 50%. [0003] Immune checkpoint Immune checkpoint mainly refers to co-inhibitory molecules and co-stimulatory molecules on T cells, which play a physiological role in maintaining self-tolerance and can help tumors escape in the tumor microenvironment. Among them, programmed cell death receptor-1 (PD-1) is an important immune checkpoint....

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61P35/02C12N5/0783C12Q1/02
CPCA61K39/3955A61K45/00A61P35/02G01N33/5011C12N5/0636
Inventor 杨林温春媚游凤涛
Owner PERSONGEN BIOMEDICINESUZHOUCO
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com