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Overview

Tags

Immune System Diseases

Hemic and Lymphatic Diseases

Neoplasms

Antibody drug conjugate (ADC)

Monoclonal antibody

Antibody

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Immune System Diseases	3
Hemic and Lymphatic Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Antibody	1
Antibody drug conjugate (ADC)	1
Monoclonal antibody	1

Top 5 Target	Count

CD163(Scavenger receptor cysteine-rich type 1 protein M130)	1
IgE(Immunoglobulin E)	1
nAChRs(Nicotinic receptors)	1

High numbers of membrane immunoglobulin E (IgE)-positive cells are characteristic of allergic conditions, atopic dermatitis, or IgE myeloma. Antibodies targeting the extracellular membrane-proximal domain of the membranous IgE-B-cell receptor (BCR) fragment can be used for specific depletion of IgE-BCR-positive cells. In this study, we derivatized such an antibody with a toxin and developed an antibody-drug conjugate (ADC) that showed strong cytotoxicity for an IgE-positive target cell line. Site-specific conjugation with maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl-auristatin E via a newly introduced single cysteine residue was used to prepare a compound with a drug-antibody ratio of 2 and favorable biophysical properties. The antibody was rapidly taken up by the target cells, showing almost complete internalization after 4 h of treatment. Its cytotoxic effect was potentiated upon cross-linking mediated by an anti-human IgG F(ab')₂ fragment. Because of its fast internalization and strict target specificity, this antibody-drug conjugate presents a valuable starting point for the further development of an anti-IgE cell-depleting agent, operating by the combined action of receptor cross-linking and toxin-mediated cytotoxicity.

01 Jul 2020·Neurobiology of DiseaseQ2 · MEDICINE

Inhibiting cellular uptake of mutant huntingtin using a monoclonal antibody: Implications for the treatment of Huntington's disease

Q2 · MEDICINE

Article

Author: Staffler, Guenther ; David, Linda Suzanne ; Salhat, Nina ; Southwell, Amber L ; Balazs, Katja ; Burkert, Markus ; Parth, Michela ; Maxan, Alexander ; Pankevych, Halyna ; Bartl, Stefan ; Siddu, Alberto ; Hayden, Michael R ; Friedrich, Theresa ; Cicchetti, Francesca ; Oueslati, Abid ; Mairhofer, Andreas ; Smrzka, Oskar W

Huntington's disease (HD) is caused by a highly polymorphic CAG trinucleotide expansion in the gene encoding for the huntingtin protein (HTT). The resulting mutant huntingtin protein (mutHTT) is ubiquitously expressed but also exhibits the ability to propagate from cell-to-cell to disseminate pathology; a property which may serve as a new therapeutic focus. Accordingly, we set out to develop a monoclonal antibody (mAB) targeting a particularly exposed region close to the aa586 caspase-6 cleavage site of the HTT protein. This monoclonal antibody, designated C6-17, effectively binds mutHTT and is able to deplete the protein from cell culture supernatants. Using cell-based assays, we demonstrate that extracellular secretion of mutHTT into cell culture media and its subsequent uptake in recipient HeLa cells can be almost entirely blocked by mAB C6-17. Immunohistochemical stainings of post-mortem HD brain tissue confirmed the specificity of mAB C6-17 to human mutHTT aggregates. These findings demonstrate that mAB C6-17 not only successfully engages with its target, mutHTT, but also inhibits cell uptake suggesting that this antibody could interfere with the pathological processes of mutHTT spreading in vivo.

100 Deals associated with Ablevia biotech GmbH

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100 Translational Medicine associated with Ablevia biotech GmbH

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Pipeline

Pipeline Snapshot as of 23 Dec 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Discovery

2

1

Preclinical

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

15cl12*tox ( IgE )	Multiple Myeloma More	Preclinical
WO2022063880 ( nAChRs )	Immune System Diseases More	Discovery
WO2022063879 ( CD163 )	Immune System Diseases More	Discovery