Ex vivo mass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker
Articolo
Data di Pubblicazione:
2023
Citazione:
Ex vivo mass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker / L. BISBAL LOPEZ, D. Ravazza, M. Bocci, A. Zana, L. Principi, S. Dakhel Plaza, A. Galbiati, E. Gilardoni, J. Scheuermann, D. Neri, L. Pignataro, C. Gennari, S. Cazzamalli, A. DAL CORSO. - In: FRONTIERS IN PHARMACOLOGY. - ISSN 1663-9812. - 14:(2023 Dec 06), pp. 1-9. [10.3389/fphar.2023.1320524]
Abstract:
Immune-stimulating antibody conjugates (ISACs) equipped with imidazoquinoline (IMD) payloads can stimulate endogenous immune cells to kill cancer cells, ultimately inducing long-lasting anticancer effects. A novel ISAC was designed, featuring the IMD Resiquimod (R848), a tumor-targeting antibody specific for Carbonic Anhydrase IX (CAIX) and the protease-cleavable Val-Cit-PABC linker. In vitro stability analysis showed not only R848 release in the presence of the protease Cathepsin B but also under acidic conditions. The ex vivo mass spectrometry-based biodistribution data confirmed the low stability of the linker-drug connection while highlighting the selective accumulation of the IgG in tumors and its long circulatory half-life.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
L. BISBAL LOPEZ, D. Ravazza, M. Bocci, A. Zana, L. Principi, S. Dakhel Plaza, A. Galbiati, E. Gilardoni, J. Scheuermann, D. Neri, L. Pignataro, C. Gennari, S. Cazzamalli, A. DAL CORSO
Link alla scheda completa: