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

Engineered regulatory t cells

An engineering and regulatory technology, applied in animal cells, vertebrate cells, genetically modified cells, etc., can solve problems such as impaired regeneration ability and liver cell aging

Pending Publication Date: 2022-06-03
KING'S COLLEGE LONDON
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the setting of chronic immune-mediated injury, hepatocytes undergo senescence and their ability to regenerate is impaired, which leads to the development of liver failure and results in significant patient morbidity and mortality (Aravinthan, A.D. and Alexander, G.J., 2016. Journal of Hepatology, 65(4), pp. 825-834)
Furthermore, liver regeneration in response to immune-mediated injury is adversely affected, leading to cirrhosis and liver cancer (Michalopoulos, G.K., 2017. Hepatology, 65(4), pp. 1384-1392)

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
  • Engineered regulatory t cells
  • Engineered regulatory t cells
  • Engineered regulatory t cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0628] Example 1 - Design of anti-ASGR1 CAR constructs

[0629] Chimeric antigen receptors (CARs) are designed to contain: an antigen recognition domain derived from a single domain antibody (sdAb) known to specifically bind ASGR; a transmembrane domain (TM) derived from CD28 (pp. 153 to 179) amino acid); and an intracellular signaling domain comprising the CD3ζ signaling domain and the CD28 signaling domain. Exemplary constructs are as follows and figure 1 shown.

[0630] Comprising: CD8 leader, ASGR1 VH antigen recognition domain, CD8α hinge domain, CD28 transmembrane, CD28 cytoplasmic signaling domain, CD3z cytoplasmic signaling domain, FP2A domain, anti-ASGR1 CAR construct 1 of GFP (SEQ ID NO:151)

[0631] MALPVTALLLPLALLLHAARPEVQLLESGGGLVQPGGSLRLSCAASGFTFEKYAMAWVRQAPGKGLEWVSRISARGVTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKHKRHEHTRFDSWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQ...

Embodiment 2

[0634] Example 2 - Generation of anti-ASGR1 CAR-Tregs

[0635] Anti-ASGR1 CAR-Tregs were generated. The isolated CD4+CD25 高 CD127- was isolated and activated with anti-CD3 / CD28 beads. Two days after activation, Tregs were transduced with lentiviruses containing an anti-ASGR1 CAR and a GFP reporter gene. Transduced and untransduced Tregs were cultured for 10 days and GFP was measured to assess transduction efficiency. figure 2 It is shown that 67.3% of the transduced Tregs expressed GFP (ie contained the anti-ASGR1 CAR construct).

Embodiment 3

[0636] Example 3 - Validation of ASGR1 expression on HepG2 cell line

[0637] HepG2 cells are an in vitro model system suitable for studying polarized human hepatocytes. ASGR1 expression in HepG2 was confirmed by FACS and compared with K562 cells, an immortalized human myeloid leukemia cell line. image 3 ASGR1 is shown to be highly expressed in HepG2 cells. HepG2 cells will be used as CAR-Treg target cells in the following experiments

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 present invention provides an engineered regulatory T cell (Treg) comprising a chimeric antigen receptor (CAR) wherein the CAR comprises an antigen recognition domain that specifically binds to an asialoglycoprotein receptor (ASGR). The present invention also provides a method of promoting liver tissue repair and / or regeneration in a subject comprising the step of administering to the subject an engineered Treg comprising a CAR or a pharmaceutical composition comprising the engineered Treg wherein the CAR comprises a liver-specific antigen recognition domain.

Description

technical field [0001] The present invention relates to engineered regulatory T cells and the therapeutic use of such cells in immune-mediated liver injury. In particular, the present invention relates to engineered regulatory T cells capable of recognizing hepatocytes, treating and / or preventing transplant rejection or immune-mediated injury, and promoting hepatocyte regeneration. Background technique [0002] The liver is an important organ that supports almost every other organ in the body. Due to its critical location and vital functions, the liver is prone to disease, especially immune-mediated damage. Worldwide, approximately 2 million people die each year from liver disease, including 1 million from complications of cirrhosis and 1 million from viral hepatitis and hepatocellular carcinoma. Liver cirrhosis is currently the 11th most common cause of death globally. Cirrhosis is the top 20 cause of DALYs and life years lost, accounting for 1.6% and 2.1% of the worldwi...

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
IPC IPC(8): C12N5/10C07K19/00C12N15/62A61K39/00A61P1/16
CPCC12N5/0637C07K16/2851C07K14/7051A61P1/16C12N2510/00C07K2319/03C07K2319/33C07K2317/622C07K2317/92C07K2317/569C07K2317/565C07K2317/55A61K2039/577A61K39/4621A61K39/464402A61K39/4611A61K39/464419A61K39/4631Y02A50/30A61K2039/515A61P37/06A61K35/17C07K14/4702C07K14/70517C07K14/70521C07K2317/24C07K2317/31C07K2317/53C12N2502/30
Inventor M·马丁内斯-洛德拉A·桑切斯-富尤
Owner KING'S COLLEGE LONDON
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