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Fusion proteins of mannose binding lectins for treatment of disease

A fusion protein and lectin technology, which is applied in the field of mannose-binding lectin fusion proteins for the treatment of diseases, can solve the problems of unsatisfactory induction of immune response and antibody generation, and harmful vaccine effects.

Inactive Publication Date: 2010-12-15
ANAPHORE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods are not designed to initiate complement activation
Indeed, complement activation would be detrimental to vaccine efficacy as it would lead to killing of the desired immune cells that had bound the MBL fusion protein
In this application, MBP was used to mediate complement activation, however, it is highly suboptimal for the induction of immune responses and antibody production

Method used

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  • Fusion proteins of mannose binding lectins for treatment of disease
  • Fusion proteins of mannose binding lectins for treatment of disease
  • Fusion proteins of mannose binding lectins for treatment of disease

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0108] Preparation of fusion protein

[0109] The fusion protein of the present invention can be expressed in any suitable standard protein expression system by culturing a host transformed with a vector encoding the fusion protein under conditions capable of expressing the fusion protein. Preferably, the expression system is one in which the desired protein can be easily isolated and refolded in vitro. In general, prokaryotic expression systems are preferred because of higher protein yields and efficient purification and refolding strategies. Accordingly, selection of appropriate expression systems, including vectors and cell types, is within the purview of those skilled in the art. Likewise, once the original amino acid sequence for a fusion protein of the present invention is selected, one skilled in the art can take into account factors such as codon bias in the selected host, the need for a secretory signal sequence in the host, and protease cleavage sites within the sig...

Embodiment 1

[0124] Example 1: Construction and expression of labeled and unlabeled MBP-CD 209 CTLD fusion protein expression plasmid clones in HEK293 cells

[0125] DC-SIGN (dendritic cell-specific ICAM-3 binding non-integrin) is a type II transmembrane protein belonging to the C-type lectin family. This protein is expressed peripherally on the surface of dendritic cells (DCs) and is involved in the initial contact between antigen presenting cells and resting T cells in the lymphatic system through ICAM-3 on T cells. DC-SIGN also interacts with ICAM-2 on epithelial cells during DC migration to lymphoid tissues. DC-SIGN also strongly binds to the HIV envelope protein gp120 and promotes viral infection in trans CD4+ T cells. The DC-Sign protein consists of a short amino-terminal cytoplasmic tail, a transmembrane domain, a stalk of up to 71 / 2 repeats, followed by a C-terminal C-type carbohydrate recognition domain (CRD). The stem promotes the formation of tetramers (coiled coils). DC-SIGN...

Embodiment 2

[0131] Example 2: with immobilized HSA-Le y or Le of cells expressing the human breast cancer cell line SKBR-3 y Analysis of Bound Various Tagged MBP-CD209CTLD Fusion Proteins

[0132] After 4 days of transient expression, expression plasmids from MBP / DC-SIGN CTLD with markers (pMBP / DC-SIGN CTLD-Abs, pMBP / DC-SIGN CTLD-ACs, pMBP / DC-SIGN CTLD-ADs, pMBP / DC -SIGN CTLD-ABsC, pMBP / DC-SIGN CTLD-ACsC, pMBP / DC-SIGN CTLD-ADsC, pMBP / DC-SIGN CTLD-FE, pMBP / DC-SIGN CTLD-GE, and pMBP / DC-SIGN CTLD-HE ) transfected HEK293 cell culture supernatants were analyzed for their binding to immobilized Le y or expressing Le of the human breast cancer cell line SKBR-3 y Ability. The MBP / DC-SIGN CTLD Abs and MBP / DC-SIGN CTLD AbsC fusion proteins were also tested for their binding to MCF-7 human breast cancer cells, LNCap prostate cancer cells, and A431 skin epithelial squamous cell carcinoma cells ability.

[0133] In the first test, 0.5 μg Le in PBS (10 mM sodium phosphate, pH 7.4, 100 mM NaCl) y...

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Abstract

Fusion proteins having sequences that target specific moieties such as carbohydrates, lipids, and / or proteins that are associated with certain cell types and / or pathogens; and a sequence that induces effector function are provided. The disclosure also provides nucleic acids encoding the fusion proteins, as well as pharmaceutical compositions, methods of use, and methods of treating conditions or diseases such as infectious diseases, cancers, immune related disorders and other ailments, that include the fusions proteins described herein.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of US Provisional Patent Application Serial No. 60 / 996,288, filed November 9, 2007, which is hereby incorporated by reference. technical field [0003] The present invention relates to the treatment of various diseases and infections. More specifically, the present invention relates to fusion proteins comprising a mannose-binding lectin polypeptide sequence. The fusion proteins can be used in pharmaceutical compositions for the treatment of infectious diseases, cancer, immune-related disorders and other ailments. Background technique [0004] Mannose-binding lectin (MBL), also known as mannose-binding protein (MBP), is a calcium-dependent serum protein that binds to sugars on the surface of a wide range of pathogens (viruses, bacteria, fungi, protozoa) Plays a role in the innate immune response by activating the complement system on the surface of pathogens. [0005] Mannose-bindin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47C12N15/09
CPCC07K2319/74C07K14/4726C07K2319/73A61P31/00A61P31/04A61P31/10A61P31/12A61P33/02A61P35/00A61P37/04
Inventor 马杰布里特·H·基尼布米凯尔·H·安德森迈克尔·埃策罗特索尔·L·霍尔蒂特
Owner ANAPHORE INC
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