A1 Refereed original research article in a scientific journal
Humanization, Radiolabeling and Biodistribution Studies of an IgG(1)-Type Antibody Targeting Uncomplexed PSA for Theranostic Applications
Authors: Strand Joanna, Sjöström Kjell, Lamminmäki Urpo J, Timmermand Oskar Vilhelmsson, Strand Sven-Erik, Tran Thuy A
Publisher: MDPI
Publishing place: Basel
Publication year: 2021
Journal: Pharmaceuticals
Journal name in source: PHARMACEUTICALS
Journal acronym: PHARMACEUTICALS-BASE
Article number: ARTN 1251
Volume: 14
Issue: 12
Number of pages: 12
eISSN: 1424-8247
DOI: https://doi.org/10.3390/ph14121251
Web address : https://doi.org/10.3390/ph14121251
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/68743365
Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A"-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications.
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