Engineered modular recombinant transporters: application of new platform for targeted radiotherapeutic agents to alpha-particle emitting 211 At.

International Journal of Radiation Oncology, Biology, Physics
Andrey A RosenkranzAlexander S Sobolev

Abstract

To generate and evaluate a modular recombinant transporter (MRT) for targeting 211 At to cancer cells overexpressing the epidermal growth factor receptor (EGFR). The MRT was produced with four functional modules: (1) human epidermal growth factor as the internalizable ligand, (2) the optimized nuclear localization sequence of simian vacuolating virus 40 (SV40) large T-antigen, (3) a translocation domain of diphtheria toxin as an endosomolytic module, and (4) the Escherichia coli hemoglobin-like protein (HMP) as a carrier module. MRT was labeled using N-succinimidyl 3-[211 At]astato-5-guanidinomethylbenzoate (SAGMB), its 125 I analogue SGMIB, or with 131 I using Iodogen. Binding, internalization, and clonogenic assays were performed with EGFR-expressing A431, D247 MG, and U87MG.wtEGFR human cancer cell lines. The affinity of SGMIB-MRT binding to A431 cells, determined by Scatchard analysis, was 22 nM, comparable to that measured before labeling. The binding of SGMIB-MRT and its internalization by A431 cancer cells was 96% and 99% EGFR specific, respectively. Paired label assays demonstrated that compared with Iodogen-labeled MRT, SGMIB-MRT and SAGMB-MRT exhibited more than threefold greater peak levels and durations of intracell...Continue Reading

References

Aug 15, 1997·The Journal of Biological Chemistry·T V AkhlyninaA S Sobolev
Apr 15, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andrey A RosenkranzAlexander S Sobolev
Feb 18, 2004·Nature Reviews. Cancer·Carmel Mothersill, Colin B Seymour
Nov 3, 2006·Cancer Research·Dinara G GilyazovaAlexander S Sobolev
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Citations

Jan 13, 2010·Journal of Oncology·Reema ZeineldinLaurie G Hudson
Apr 8, 2009·Critical Reviews in Immunology·Hideho OkadaMitsugu Fujita
Feb 22, 2012·International Journal of Nanomedicine·Tatiana A SlastnikovaAlexander S Sobolev
Jun 8, 2012·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Hetal Pandya, Waldemar Debinski
Aug 8, 2009·AJNR. American Journal of Neuroradiology·J J CuaronA E Hirsch
Jun 4, 2013·Immunotherapy·Pasquale De BonisAnnunziato Mangiola
Nov 12, 2014·Biochemistry. Biokhimii︠a︡·A A RosenkranzA S Sobolev
Jan 19, 2018·Annual Review of Biomedical Engineering·Michael R McDevittStavroula Sofou
Aug 29, 2020·International Journal of Radiation Biology·Andrey A RosenkranzAlexander S Sobolev
May 21, 2018·Doklady. Biochemistry and Biophysics·T R KamaletdinovaA S Sobolev
Nov 9, 2018·Frontiers in Pharmacology·Tatiana A SlastnikovaA S Sobolev
May 21, 2018·Doklady. Biochemistry and Biophysics·A V UlasovA S Sobolev
Dec 3, 2020·Acta Crystallographica. Section D, Structural Biology·Yuri V KhramtsovAlexander S Sobolev
Oct 15, 2020·Biochemistry. Biokhimii︠a︡·A A Rosenkranz, T A Slastnikova
Jun 14, 2021·Critical Reviews in Oncology/hematology·Yanrui LiEva Bezak

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