ArticleProtein engineering, design & selection : PEDS2004
Covalent disulfide-linked anti-CEA diabody allows site-specific conjugation and radiolabeling for tumor targeting applications.
Article in Protein engineering, design & selection : PEDS, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 111 citations in OpenAlex.
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- Development of Anti-LRRC15 Small Fragments for Imaging Purposes Using a Phage-Display ScFv Approach.International journal of molecular sciences · 2022Article
- ImmunoPET: harnessing antibodies for imaging immune cells.Molecular imaging and biology · 2022Review
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- ImmunoPET: Concept, Design, and Applications.Chemical reviews · 2020Review
- Tri-functional platform for construction of modular antibody fragments forChemical science · 2020Article
- A Dual-Modality Linker Enables Site-Specific Conjugation of Antibody Fragments forJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Article
- Tumor Imaging Using Radiolabeled Matrix Metalloproteinase-Activated Anthrax Proteins.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Article
- Site-Specific Fluorescent Labeling of Antibodies and Diabodies Using SpyTag/SpyCatcher System for In Vivo Optical Imaging.Molecular imaging and biology · 2019Article
- Emerging Fluorescent Molecular Tracers to Guide Intra-Operative Surgical Decision-Making.Frontiers in pharmacology · 2019Review
- Antibody Fragment and Affibody ImmunoPET Imaging Agents: Radiolabelling Strategies and Applications.ChemMedChem · 2018Review
- ImmunoPET Imaging of αMolecular imaging and biology · 2018Article
- Cerenkov Luminescence Imaging as a Modality to Evaluate Antibody-Based PET Radiotracers.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2017Article
- Fluorescent Image-Guided Surgery with an Anti-Prostate Stem Cell Antigen (PSCA) Diabody Enables Targeted Resection of Mouse Prostate Cancer Xenografts in Real Time.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Development of PF-06671008, a Highly Potent Anti-P-cadherin/Anti-CD3 Bispecific DART Molecule with Extended Half-Life for the Treatment of Cancer.Antibodies (Basel, Switzerland) · 2016Article
- Site-Specifically Labeled Immunoconjugates for Molecular Imaging--Part 1: Cysteine Residues and Glycans.Molecular imaging and biology · 2016Review
- Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
An engineered anti-carcinoembryonic antigen (CEA) diabody (scFv dimer, 55 kDa) was previously constructed from the murine anti-CEA T84.66 antibody. Tumor targeting, imaging and biodistribution studies in nude mice bearing LS174T xenografts with radiolabeled anti-CEA diabody demonstrated rapid tumor uptake and fast blood clearance, which are favorable properties for an imaging agent. Current radiolabeling approaches result in random modification of the protein surface, which may impair immunoreactivity especially for smaller antibody fragments. Site-specific conjugation approaches can direct modifications to reactive groups located away from the binding site. Here, cysteine residues were introduced into the anti-CEA diabody at three different locations, to provide specific thiol groups for chemical modification. One version (with a C-terminal Gly-Gly-Cys) existed exclusively as a disulfide-bonded dimer. This cysteine-modified diabody (Cys-diabody) retained high binding to CEA and demonstrated tumor targeting and biodistribution properties identical to the non-covalent diabody. Furthermore, following reduction of the disulfide bond, the Cys-diabody could be chemically modified using a thiol-specific bifunctional chelating agent, for radiometal labeling. Thus, the Cys-diabody provides a covalently linked alternative to conventional diabodies, which can be reduced and modified site-specifically. This format will provide a versatile platform for targeting a variety of agents to CEA-positive tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.