| Autor: |
Mikitiuk M; Recepton Sp. z o.o., Trzy Lipy 3, 80-172 Gdańsk, Poland.; Department of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdansk, Abrahama 58, 80-307 Gdańsk, Poland., Barczyński J; Recepton Sp. z o.o., Trzy Lipy 3, 80-172 Gdańsk, Poland.; Department of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdansk, Abrahama 58, 80-307 Gdańsk, Poland., Bielski P; Recepton Sp. z o.o., Trzy Lipy 3, 80-172 Gdańsk, Poland., Arciniega M; Recepton Sp. z o.o., Trzy Lipy 3, 80-172 Gdańsk, Poland., Tyrcha U; Recepton Sp. z o.o., Trzy Lipy 3, 80-172 Gdańsk, Poland., Hec A; Recepton Sp. z o.o., Trzy Lipy 3, 80-172 Gdańsk, Poland., Lipińska AD; Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, 80-307 Gdańsk, Poland., Rychłowski M; Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, 80-307 Gdańsk, Poland., Holak TA; Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland., Sitar T; Recepton Sp. z o.o., Trzy Lipy 3, 80-172 Gdańsk, Poland. |
| Abstrakt: |
Lysosome-targeting chimeras (LYTACs) have recently been developed to facilitate the lysosomal degradation of specific extracellular and transmembrane molecular targets. However, the LYTAC particles described to date are based on glycopeptide conjugates, which are difficult to prepare and produce on a large scale. Here, we report on the development of pure protein LYTACs based on the non-glycosylated IGF2 peptides, which can be readily produced in virtually any facility capable of monoclonal antibody production. These chimeras utilize the IGF2R/CI-M6PR pathway for lysosomal shuttling and, in our illustrative example, target programmed death ligand 1 (PD-L1), eliciting physiological effects analogous to immune checkpoint blockade. Results from in vitro assays significantly exceed the effects of anti-PD-L1 antibodies alone. |
