Calicheamicin Antibody-Drug Conjugates with Improved Properties.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
29
04
2020
revised:
02
09
2020
accepted:
26
02
2021
pubmed:
17
3
2021
medline:
27
1
2022
entrez:
16
3
2021
Statut:
ppublish
Résumé
Calicheamicin antibody-drug conjugates (ADCs) are effective therapeutics for leukemias with two recently approved in the United States: Mylotarg (gemtuzumab ozogamicin) targeting CD33 for acute myeloid leukemia and Besponsa (inotuzumab ozogamicin) targeting CD22 for acute lymphocytic leukemia. Both of these calicheamicin ADCs are heterogeneous, aggregation-prone, and have a shortened half-life due to the instability of the acid-sensitive hydrazone linker in circulation. We hypothesized that we could improve upon the heterogeneity, aggregation, and circulation stability of calicheamicin ADCs by directly attaching the thiol of a reduced calicheamicin to an engineered cysteine on the antibody via a disulfide bond to generate a linkerless and traceless conjugate. We report herein that the resulting homogeneous conjugates possess minimal aggregation and display high
Identifiants
pubmed: 33722856
pii: 1535-7163.MCT-20-0035
doi: 10.1158/1535-7163.MCT-20-0035
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Calicheamicins
0
Immunoconjugates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1112-1120Informations de copyright
©2021 American Association for Cancer Research.
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