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.

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]

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

L. BISBAL LOPEZ
Primo
;
A. Galbiati;E. Gilardoni;L. Pignataro;C. Gennari;A. DAL CORSO
Ultimo
2023

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.
English
Settore CHIM/06 - Chimica Organica
Articolo
Esperti non anonimi
Pubblicazione scientifica
   Small-Molecule Drug Conjugates for Targeted Delivery in Tumor Therapy (Magicbullet Reloaded)
   Magicbullet Reloaded
   EUROPEAN COMMISSION
   H2020
   861316
6-dic-2023
Frontiers Media
14
1
9
9
Pubblicato
Periodico con rilevanza internazionale
https://www.frontiersin.org/articles/10.3389/fphar.2023.1320524/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Pharmacology&id=1320524
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info:eu-repo/semantics/article
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]
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Prodotti della ricerca::01 - Articolo su periodico
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262
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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. Gen...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1019769
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