Frontiers in Pharmacology (Dec 2023)

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

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

DOI
https://doi.org/10.3389/fphar.2023.1320524
Journal volume & issue
Vol. 14

Abstract

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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.

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