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

Sialylated di-Lewis alpha expressed on glycoproteins instead of glycolipids and antibodies thereof as functional cancer targets

A sialylation, glycoprotein technology, applied in the direction of anti-animal/human immunoglobulin, antibody, immunoglobulin, etc., can solve problems such as unacceptable normal distribution

Active Publication Date: 2022-03-29
SCANCELL
View PDF24 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

antisialylated Lewis a MAbs may have an unacceptably normal distribution, which is supported by observations of GivaRex, a mouse monoclonal antibody, and whose patent (WO0191792) was abandoned in preclinical studies

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
  • Sialylated di-Lewis alpha expressed on glycoproteins instead of glycolipids and antibodies thereof as functional cancer targets
  • Sialylated di-Lewis alpha expressed on glycoproteins instead of glycolipids and antibodies thereof as functional cancer targets
  • Sialylated di-Lewis alpha expressed on glycoproteins instead of glycolipids and antibodies thereof as functional cancer targets

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0184] Generation and preliminary characterization of FG129mAb

[0185] FG129 was produced by immunizing Balb / c mice at 2-month intervals with plasma membrane lipid extracts of LS180 cells (colorectal cell line) incorporated into liposomes using α - Galactosylceramide as adjuvant in the first, third and fourth immunizations, anti-CD40 mAb as adjuvant during the second immunization.

[0186] Analysis of antibody responses to immunization: Antibody titers were first monitored by lipid enzyme-linked immunosorbent assay (ELISA). Flow cytometric analysis (FACS) was performed using LS180 tumor cells and Western blot using LS180. Mice considered to have the best response were boosted intravenously (i.v.) with LS180 plasma membrane lipid extract before fusion compared to prebleed serum controls. Eight days after fusion, supernatants were collected and screened for fresh LS180 tumor cells by flow cytometry. Hybridomas demonstrating cell surface binding using indirect immunofluoresce...

Embodiment 2

[0188] Chimerism of FG129

[0189] The term "chimeric antibody" is intended to mean an antibody in which the variable region sequences are derived from one species and the constant region sequences are derived from another species, for example, in which the variable region sequences are derived from a mouse antibody and the constant region sequences are derived from a human antibody. Antibody. Chimeric (or humanized) antibodies of the invention can be prepared based on the sequence of the murine mAb prepared as described above. The heavy chain of FG129mAb is shown in Fig. 1 ( Figure 1a ) and light chain ( Figure 1b The amino acid and nucleotide sequences of the variable and constant regions of ). Numbers refer to the standardized IMGT system used for numbering antibody sequences [49]. CDR1, CDR2 and CDR3 regions are indicated. The FG129 heavy chain belongs to the mouse heavy chain family IGHV10-1*02 (IGHD1-1*01, IGHJ4*01) and has three mutations compared to the parental ...

Embodiment 3

[0192] Definition of epitopes recognized by FG129 and CH129 mAbs

[0193] MAb FG129 is a mouse IgGlk isotype produced by immunizing Balb / c mice with glycolipid extracts from the colorectal cell line LS180. Glycan profiling of ≥600 natural and synthetic glycans by CFG shows that FG129 binds sialylated di-Lewis a (100%) and sialylated Lewis a-x High specificity (89%). It can also be associated with monosialylated Lewis a (89%) bound, but only on the long vector (sp8) but not on the short vector (sp0), indicating that at least 4 carbohydrates or enough space is required to allow insertion of three carbohydrate residues for proper binding Conformation exists in the antibody sequence ( Figure 3a ).

[0194] To analyze whether these glycans are expressed on glycoproteins or glycolipids from tumor cell lines, FG129 binding was assessed by Western blotting ( Figure 3b ). Tumor lysates or tumor glycolipid extracts from colorectal (Colo205HCT-15 and LS180) and pancreatic cell l...

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

PropertyMeasurementUnit
affinityaaaaaaaaaa
affinityaaaaaaaaaa
affinityaaaaaaaaaa
Login to View More

Abstract

The present invention relates to the ability to bind sialylated di-Lewis a Isolated specific binding members of the invention, and related therapeutic and pharmaceutical compositions for the treatment of cancer.

Description

technical field [0001] The present invention relates to sialylated di-Lewis a (sialyl-di-Lewis a ) targeting and binding members in cancer, such as monoclonal antibodies (mAbs), which bind the glycans expressed on glycoproteins but not lipids. Background technique [0002] Glycan structures exist on protein and glycolipid backbones and can be massively overexpressed in cancer due to altered expression of glycosyltransferases. Proteins in the ER are branched with 9-mannose (man) during N-linked glycosylation 9 Complex modification. When the protein leaves the ER, mannosidase I removes mannose (man) 5 4 in , then mannosidase II removes the other 2 (man) 3 . Glycosyltransferases then build complex glycan structures on this mannose core. These glycans are critical for protein folding and function. Generating mAbs to glycans expressed on proteins is a problem because mAbs rarely see only small glycans, but usually recognize glycans on proteins giving very stringent expres...

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 Patents(China)
IPC IPC(8): C07K16/28C07K16/30A61P35/00
CPCC07K16/2896C07K16/3023C07K16/303C07K16/3046C07K16/3069A61K2039/505C07K2317/24C07K2317/30C07K2317/622C07K2317/732C07K2317/734C07K2317/77C07K2317/92A61K47/6857A61K47/6859A61K47/6863A61K47/6869A61K47/6849A61P35/00C07K2319/03C07K14/7051A61K2039/5158A61K2039/5156A61K39/0011A61K47/68031A61K47/68033A61K47/6851C07K16/2809C07K16/30C07K2317/31A61K39/39558A61K47/6803
Inventor L·G·达兰特M·范客美尔贝克S·蒂瓦达T·帕森斯R·麦金托什
Owner SCANCELL
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