AUTHOR=Bisbal Lopez Lydia , Ravazza Domenico , Bocci Matilde , Zana Aureliano , Principi Lucrezia , Dakhel Plaza Sheila , Galbiati Andrea , Gilardoni Ettore , Scheuermann Jörg , Neri Dario , Pignataro Luca , Gennari Cesare , Cazzamalli Samuele , Dal Corso Alberto 

TITLE=Ex vivo mass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1320524

DOI=10.3389/fphar.2023.1320524

ISSN=1663-9812

ABSTRACT=<p>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. <italic>In vitro</italic> stability analysis showed not only R848 release in the presence of the protease Cathepsin B but also under acidic conditions. The <italic>ex vivo</italic> 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.</p>