Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance.
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An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP).
The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP.
The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery.
Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to an LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery.
Nuclear medicine and biology. 2017 Jan 17 [Epub ahead of print]
Patty Wong, Lin Li, Junie Chea, Melissa K Delgado, Desiree Crow, Erasmus Poku, Barbara Szpikowska, Nicole Bowles, Divya Channappa, David Colcher, Jeffrey Y C Wong, John E Shively, Paul J Yazaki
Department of Radiation Oncology, City of Hope Medical Center, City of Hope, Duarte, CA, 91010-3000, USA., Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA., Department of Molecular Immunology, Beckman Research Institute, City of Hope, Duarte, CA, 91010-3000, USA. Electronic address: .