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

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

  • Front Pharmacol. 2023 Dec 6:14:1320524. doi: 10.3389/fphar.2023.1320524.
Lydia Bisbal Lopez 1,  Domenico Ravazza 2,  Matilde Bocci 2,  Aureliano Zana 2,  Lucrezia Principi 2,  Sheila Dakhel Plaza 2,  Andrea Galbiati 2,  Ettore Gilardoni 2,  Jörg Scheuermann 3,  Dario Neri 2 3 4,  Luca Pignataro 1,  Cesare Gennari 1,  Samuele Cazzamalli 2,  Alberto Dal Corso 1
Affiliations

Affiliations

  • 1 Chemistry Department, Università degli Studi di Milano, Milano, Italy.
  • 2 R&D Department, Philochem AG, Otelfingen, Switzerland.
  • 3 Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland.
  • 4 Philogen S.p.A, Siena, Italy.
PMID: 38125888 DOI: 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.

Keywords

Resiquimod; immune stimulating antibody conjugates; prodrugs; quantitative biodistribution; toll-like receptors.

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