Abstract |
Antibody-drug conjugates are generally believed to crucially rely on internalization into cancer cells for therapeutic activity. Here, we show that a non-internalizing antibody-drug conjugate, based on the F16 antibody specific to the alternatively spliced A1 domain of tenascin-C, mediates a potent therapeutic activity when equipped with the anthracycline PNU159682. The peptide linker, connecting the F16 antibody in IgG format at a specific cysteine residue to the drug, was stable in serum but could be efficiently cleaved in the subendothelial extracellular matrix by proteases released by the dying tumor cells. The results indicate that there may be a broader potential applicability of non-internalizing antibody-drug conjugates for cancer therapy than what had previously been assumed.
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Authors | Alberto Dal Corso, Rémy Gébleux, Patrizia Murer, Alex Soltermann, Dario Neri |
Journal | Journal of controlled release : official journal of the Controlled Release Society
(J Control Release)
Vol. 264
Pg. 211-218
(Oct 28 2017)
ISSN: 1873-4995 [Electronic] Netherlands |
PMID | 28867376
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier B.V. All rights reserved. |
Chemical References |
- 3'-deamino-3'',4'-anhydro-(2''-methoxy-3''-oxy-4''-morpholinyl)doxorubicin
- Antineoplastic Agents
- Immunoconjugates
- Immunoglobulin G
- Tenascin
- Doxorubicin
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage)
- Cell Line, Tumor
- Doxorubicin
(administration & dosage, analogs & derivatives)
- Female
- Humans
- Immunoconjugates
(administration & dosage)
- Immunoglobulin G
(immunology)
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasms
(drug therapy, pathology)
- Tenascin
(immunology)
- Tumor Burden
(drug effects)
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