Evidence map›Paper›PMID 40775564›Full record

ArticleMolecular imaging and biology2025

Reengineered Anti-CD4 Cys-diabody Variants for

Felix B Salazar, Richard Tavaré, Arya Ökten, Maciej Kujawski, Anna M Wu, Kirstin A Zettlitz

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Article in Molecular imaging and biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Felix B SalazarCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0009-0004-9361-1528
Richard TavaréCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0001-5150-5963
Arya ÖktenCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-7460-7951
Maciej KujawskiDepartment of Immunology and Theranostics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.ORCID 0000-0002-9701-5211
Anna M WuCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0001-8487-823X
Kirstin A ZettlitzCrump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. kzettlitz@coh.org.ORCID 0000-0003-4870-6603

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
NCI NIH HHS P30 CA016042NIH HHS P30CA016042
6 · The paper itself

Abstract

purposeCD4 PROCEDURES: In this work, an anti-CD4 cys-diabody based on the hybridoma GK1.5 was reengineered by CDR-grafting (GK1.5 FR cDb) for higher expression in mammalian cell lines. An N-glycosylation motif in the variable light chain domain framework was removed by site-directed mutagenesis, resulting in GK1.5 N80D cDb. To investigate the impact of the variable domain glycan on the in vivo biodistribution and pharmacokinetics, both cys-diabodies were site-specifically conjugated with deferoxamine-maleimide and radiolabeled by chelation of zirconium-89. Serial immunoPET/CT imaging was used for non-invasive, whole-body assessment of specific targeting, biodistribution, and differential clearance of the two novel anti-CD4 cys-diabodies.

resultsThe anti-CD4 cys diabody was successfully re-engineered by CDR-grafting (GK1.5 FR cDb) and aglycosylation (GK1.5 N80D cDb), resulting in a higher expression yield (~ tenfold increase) without impacting antigen specificity or affinity. Both cys-diabody variants were successfully

conclusionThe novel reengineered anti-CD4 GK1.5 N80D cDb overcomes the previous production yield bottleneck and provides same-day

Indexed as

CD4 AntigensCD4-Positive T-LymphocytesCysteinePositron-Emission TomographyRadioisotopesZirconiumAnimalsFemaleMiceTissue DistributionCD4 AntigensCysteineRadioisotopesZirconiumZirconium-89Aglycosylation/glycoengineeringAntibody fragmentsCDR-graftingImmune cellsNon-invasive imagingT helper cellZirconium-89

Identifiers

PMID40775564
PMCPMC12628392

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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.