Method for promoting regeneration of functional T cells by arterial endothelium

A cell regeneration and functional technology, applied in the field of biomedicine, can solve the problems of small number of T cells and lack of function, and achieve the effect of accelerating clinical transformation, promoting economic development, and improving the differentiation potential of T cells

Active Publication Date: 2021-08-17
INST OF HEMATOLOGY & BLOOD DISEASES HOSPITAL CHINESE ACADEMY OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
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Problems solved by technology

Existing research techniques mainly focus on the second stage of T cell differentiation, while ignoring the first stage, resulting in the hematopoietic progenitor cells obtained in the first stage of differentiation being biased towards primitive hematopoiesis, which in turn leads to the number of T cells produced in the second stage of differentiation Too few, lack of full functionality

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  • Method for promoting regeneration of functional T cells by arterial endothelium
  • Method for promoting regeneration of functional T cells by arterial endothelium
  • Method for promoting regeneration of functional T cells by arterial endothelium

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Embodiment Construction

[0042] The present invention will be further described below in conjunction with specific embodiments, but does not limit the scope of the invention.

[0043] Induction and separation of autologous artery endothelium and blood endothelial cells

[0044] We use a single-layer step-by-step differentiation system for HPSC endothelial blood division, and the selected initial cells are human embryonic stem cell line H1. The culture fluid of H1 cells is E8 Medium (Life Technologies), the recovery or passage, and the Stemcell Technologies will be added and removed within 24 hours. H1 cells need to be cultured on a 1: 90 diluted Matrigel (BD). The H1 cell has a resuscitation of H1 cells rapidly from liquid nitrogen, placed rapidly in a water bath at 37 ° C; adding cells in the frozen tube to E8 Medium, then 1000 turn for 5 minutes; discard The centrifugal cell precipitate was blown by 1 ml E8 MEDIUM + Y-27632 (E8 + Y) culture solution, and finally the cell species was laid into the cultur...

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Abstract

The invention relates to a method for promoting functional T cell regeneration by arterial endothelium. In this method, the arterial endothelium promotes the regeneration of functional T cells by promoting the regeneration of hematopoietic progenitor cells with T line bias. According to the invention, the first stage of differentiation from human pluripotent stem cells (hPSC) to T cells is emphatically optimized, and it is found that the autologous artery endothelial cells derived from the hPSC can improve the T line differentiation potential of hematopoietic progenitor cells, and the T cells obtained through the autologous artery endothelial cells have the functions similar to those of normal human peripheral blood T cells. The establishment of the hPSC-T induced differentiation system can provide continuous T cell resources for chimeric antigen receptor T cell (CAR-T) treatment. Based on the verification, the CD19-CAR-T cell derived from the hPSC has a potential in-vivo and in-vitro tumor killing effect.

Description

Technical field [0001] The present invention relates to the field of biopharmaceutical, and more particularly to a method of arterial inferior promoting functional T cell regeneration. Background technique [0002] T cells are an important immune cell in the human body, which has a variety of biological functions, such as direct killing target cells, assisted or inhibiting B cells, etc., is an important cell that resists disease infections and anti-tumors. Chimeric antigen receptor T cell immunotherapy (Car-t) is a new precision targeting therapy for treating tumors, a very promising, accurate, fast, efficient, and likely to cure cancer new tumor immunity treatment method. In recent years, the CD19-CAR-T has achieved good results in clinical treatment of acute B lymphocyte leukemia (B-AL). One of the main defects currently existing in CAR-T therapy is that the number of T cells is insufficient. According to statistics, 30% -50% of patients are accompanied by T cell depletion, whi...

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Application Information

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IPC IPC(8): C12N5/0783C12N5/071
CPCC12N5/0636C12N5/069C12N2501/125C12N2501/26C12N2501/145C12N2501/2303C12N2501/165C12N2501/115C12N2501/15C12N2533/52C12N2501/727C12N2501/16C12N2501/155C12N2500/02A61K2239/38A61K39/4611A61K39/464412A61K2239/31A61K2239/48A61K39/4631C12N2502/28C12N2506/02C12N2533/90C12N2501/415C12N2500/99C07K16/2803C12N2510/00A61P35/00A61K2039/572C07K2319/03
Inventor 程涛沈俊王建祥王征宇王敏徐颖茜张朔吕淑珍
Owner INST OF HEMATOLOGY & BLOOD DISEASES HOSPITAL CHINESE ACADEMY OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
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