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Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics DCAF

Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics DCAF

Published on: September 17, 2019

A novel complement inhibitor sMAP-FH targeting both the lectin and alternative complement pathways.

Mika Takasumi^1,2, Tomoko Omori¹, Takeshi Machida¹

¹Department of Immunology, Fukushima Medical University School of Medicine, Fukushima-City, Japan.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology

|March 29, 2020

Summary

Researchers developed a novel dual complement inhibitor, sMAP-FH, which effectively blocks both the lectin and alternative pathways (LP and AP). This fusion protein shows promise as a therapeutic agent for diseases involving complement system dysregulation.

Keywords:

MAp44 alternative complement pathway factor H lectin complement pathway small mannose-binding lectin-associated protein

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Last Updated: Dec 25, 2025

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Published on: May 4, 2017

Area of Science:

Immunology
Biotechnology

Background:

Complement activation via lectin pathway (LP) and alternative pathway (AP) exacerbates diseases like ischemia-reperfusion injury and age-related macular degeneration (AMD).
Targeting these pathways offers a therapeutic strategy for various inflammatory and autoimmune conditions.

Purpose of the Study:

To develop and evaluate novel dual inhibitors targeting both LP and AP complement activation.
To assess the efficacy of fusion proteins MAp44-FH and sMAP-FH in inhibiting complement pathways.

Main Methods:

Generation of fusion proteins by combining LP regulators (MAp44, sMAP) with AP regulator domains (SCR1/5-FH).
Administration of murine fusion proteins in mice to assess complex formation with endogenous lectins.
In vitro and in vivo complement activation assays to evaluate inhibitory effects on LP and AP.

Main Results:

Both MAp44-FH and sMAP-FH fusion proteins formed complexes with endogenous lectins in mice.
sMAP-FH demonstrated significantly stronger inhibition of LP and AP activation compared to MAp44-FH, both in vitro and in vivo.
The human form of sMAP-FH effectively inhibited LP and AP activation in human sera.

Conclusions:

The novel fusion protein sMAP-FH acts as a potent dual inhibitor of both LP and AP complement activation.
sMAP-FH shows therapeutic potential for diseases where aberrant activation of both complement pathways plays a significant role.