High affinity sirp-alpha reagents

A kind of affinity, S66 technology, applied in chemical instruments and methods, biochemical equipment and methods, instruments, etc.

Active Publication Date: 2014-11-05
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
View PDF4 Cites 16 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Alternatively, blocking SIRPα recognition also allows engulfment of targets that are not normally engulfed

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
  • High affinity sirp-alpha reagents
  • High affinity sirp-alpha reagents
  • High affinity sirp-alpha reagents

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0158] High-affinity SIRPα lowers the threshold of macrophages phagocytosis of cancer cells.

[0159] The ability of tumors to evade the immune system is an emerging cancer marker, and new treatment strategies that direct the immune response to cancer cells have shown promise in experimental and clinical settings. Macrophages usually infiltrate tumors, and recent studies have identified CD47 as an anti-phagocytosis "don't eat me" signal, which is highly expressed on many types of cancer to escape macrophage-mediated destruction. Antibodies that block the binding of CD47 to the inhibitory receptor SIRPα on macrophages greatly increase the phagocytosis of cancer cells—identifying an exciting new axis for working with anti-tumor immunotherapy. Using directed evolution and protein engineering to modify the binding domain of SIRPα, its wild-type affinity is too weak to be useful as a high-affinity competitive antagonist of CD47.

[0160] We generated a variant of SIRPα that binds CD47 ...

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

High affinity SIRP-alpha reagent are provided, which (i) comprise at least one amino acid change relative to the wild-type protein; and (ii) have an increased affinity for CD47 relative to the wild-type protein. Compositions and methods are provided for modulating phagocytosis in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity SIRPalpha reagent, which blocks the physiological binding interaction between SIRPalpha and its ligand CD47.

Description

[0001] Government power [0002] The present invention was completed with government support under the contracts CA086017, HL058770 and CA139490 funded by the National Institutes of Health. The government has certain rights in the invention. Background of the invention [0003] Cell turnover begins with the induction of an apoptotic program or other cellular changes that mark them for removal, and subsequent markers are recognized by phagocytes including macrophages, dendritic cells, etc. This process requires specific and selective removal of unwanted cells. Distinguish between healthy cells and unwanted / aging / dying cells. Unwanted / aging / dying cells display a signal called "eat me", that is, a marker or ligand for "change of self". It can be recognized by receptors on phagocytes. Healthy cells can display "don't eat me" signals that actively inhibit phagocytosis; these signals are down-regulated in dying cells or exist in an altered conformation. The cell surface protein CD47 ...

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): A61K38/16
CPCA61K38/16C07K14/4703C07K16/2803C12N9/16C12Y301/03048G01N33/5005A61K38/00C07K2317/52C07K2319/30A61P35/00A61P43/00A61K38/1774
Inventor A·M·林K·C·加西亚K·A·魏斯可夫A·M·莱文I·L·威斯曼
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap