Ex vivo mass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker
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Date
2023-12-06
Publication Type
Journal Article
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yes
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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.
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published
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Journal / series
Volume
14
Pages / Article No.
1320524
Publisher
Frontiers Media
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Subject
immune stimulating antibody conjugates; Resiquimod; toll-like receptors; prodrugs; quantitative biodistribution
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Notes
Funding
861316 - Small-Molecule Drug Conjugates for Targeted Delivery in Tumor Therapy (EC)