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Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity.
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http://dx.doi.org/10.1016/j.bmcl.2017.09.065 | DOI Listing |
Acta Pharm Sin B
August 2025
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
With the advent of precision medicine and personalized treatment, targeted therapies have become pivotal in oncology. Noninvasive molecular imaging, especially immunoPET/SPECT, plays a crucial role in refining cancer diagnostics and treatment monitoring by visualizing biological processes at the molecular level. This review explores the dynamic field of immunoPET/SPECT imaging using Fab and F(ab') fragments, characterized by advantageous pharmacokinetics and swift clearance from the bloodstream, making them suitable for same-day imaging procedures.
View Article and Find Full Text PDFN Biotechnol
August 2025
Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Fukuoka 819-0395, Japan; Division of Biotechnology, Center for Future Chemistry, Kyushu University, 744 Motooka, Fukuoka 819-0395, Japan. Electronic address:
The fragment antigen-binding (Fab) fragment of IgG has been studied widely as a delivery vehicle for tumor-targeting drugs and dyes due to its high specificity and enhanced tumor penetration, which is attributed to its small size. Functionalizing Fab with chemical entities requires site-specific modification to preserve the binding ninity and ensure product homogeneity. In this study, we report a tag-free, site-specific labeling approach targeting a Lys residue in Fab using the recently developed engineered zymogen of microbial transglutaminase fused with an antibody-binding protein G.
View Article and Find Full Text PDFMol Imaging Biol
August 2025
Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, 060-0812, Japan.
Purpose: In target-specific cancer imaging, antibodies and their fragments are conjugated with fluorescent dyes to work as targeting molecules. We have recently developed indocyanine green (ICG) derivatives with anionic functional groups at the benzoindolenine moiety. When the ICG derivatives are used for antibody-based imaging, the chemical characteristics of the conjugated dyes may influence the pharmacokinetics of the targeting molecules.
View Article and Find Full Text PDFJ Nucl Med
September 2025
Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin;
Our study aimed to develop and evaluate [Cu]Cu-NOTA-EV-F(ab') for immuno-PET imaging of nectin-4 expression in triple-negative breast cancer (TNBC) and urothelial bladder cancer (UBC) models, with the goal of achieving rapid, specific tumor targeting and high tumor-to-background contrast. Bivalent antibody fragments were generated from enfortumab vedotin (EV) using IdeS protease and conjugated with NOTA for radiolabeling with Cu. In vitro binding and uptake studies were performed using TNBC and UBC cell lines.
View Article and Find Full Text PDFInt J Pharm X
December 2025
Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla 34596, Istanbul, Turkiye.
Antibody-conjugated nanoparticles (ACNPs), particularly immunoliposomes (ILs), have gained significant attention in cancer treatment due to their enhanced efficacy and superior tissue penetration. However, their high production costs and technical challenges underscore the need for more cost-effective alternatives. Niosomes, with their lower production costs, improved stability, and biocompatibility, have emerged as promising alternatives to liposomes in drug delivery.
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