Imaging · dataset · 2023
Optimization and Characterization of Novel ALCAM-Targeting Antibody Fragments for Transepithelial Delivery
Listed in ETH Zürich Research Collection
Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule that supports T cell activation, leukocyte migration, and (lymph)angiogenesis and has been shown to contribute to the pathology of various immune-mediated disorders, including asthma and corneal graft rejection.
Description
In contrast to monoclonal antibodies (mAbs) targeting ALCAM’s T cell expressed binding partner CD6, no ALCAM-targeting mAbs have thus far entered clinical development.
This is likely linked with the broad expression of ALCAM on many different cell types, which increases the risk of eliciting unwanted treatment-induced side effects upon systemic mAb application. Targeting ALCAM in surface-exposed tissues, such as the lungs or the cornea, by a topical application could circumvent this issue. Here, we report the development of various stability- and affinity-improved anti-ALCAM mAb fragments with cross-species reactivity towards mouse, rat, monkey, and human ALCAM.
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Fragments generated in either mono- or bivalent formats potently blocked ALCAM–CD6 interactions in a competition ELISA, but only bivalent fragments efficiently inhibited ALCAM–ALCAM interactions in a leukocyte transmigration assay. The different fragments displayed a clear size-dependence in their ability to penetrate the human corneal epithelium. Furthermore, intranasal delivery of anti-ALCAM fragments reduced leukocyte infiltration in a mouse model of asthma, confirming ALCAM as a target for topical application in the lungs.
Links
Where it is published
- ETH Zürich Research Collection record hdl.handle.net/20.500.11850/623373 ↗
landing page · from research collection ethz ch
- DOI doi.org/10.3929/ethz-b-000623373 ↗
DOI / persistent id · from research collection ethz ch
Catalogue records · 1
- OAI-PMH record research-collection.ethz.ch/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Awww.… ↗
metadata API · from research collection ethz ch
Topics
- From keywords
- Chemistry · Computer Science & AI · Earth & Environmental Science · Economics & Finance · Engineering · Humanities · Life Sciences · Materials Science · Mathematics & Statistics · Medicine & Health · Physics · Psychology & Behavioral Science · Social Science
- Inferred from text
- Biochemistry and cell biology 68%
Provenance · 1 source records, 19 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| ETH Zürich Research Collection | oai:www.research-collection.ethz.ch:20.500.11850/623373 | 11 d ago | JSON v1 |
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| title | source · research collection ethz ch | connector:research_collection_ethz_ch@1.0.0 | /metadata/dc/title |