Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate.
FDA
antibody-drug conjugates (ADCs)
bioconjugation
chemotherapy
cytotoxic drug
linker
monoclonal antibody
tumor
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
11 Feb 2022
11 Feb 2022
Historique:
received:
28
12
2021
revised:
27
01
2022
accepted:
04
02
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
27
2
2022
Statut:
epublish
Résumé
As one of the major therapeutic options for cancer treatment, chemotherapy has limited selectivity against cancer cells. Consequently, this therapeutic strategy offers a small therapeutic window with potentially high toxicity and thus limited efficacy of doses that can be tolerated by patients. Antibody-drug conjugates (ADCs) are an emerging class of anti-cancer therapeutic drugs that can deliver highly cytotoxic molecules directly to cancer cells. To date, twelve ADCs have received market approval, with several others in clinical stages. ADCs have become a powerful class of therapeutic agents in oncology and hematology. ADCs consist of recombinant monoclonal antibodies that are covalently bound to cytotoxic chemicals via synthetic linkers. The linker has a key role in ADC outcomes because its characteristics substantially impact the therapeutic index efficacy and pharmacokinetics of these drugs. Stable linkers and ADCs can maintain antibody concentration in blood circulation, and they do not release the cytotoxic drug before it reaches its target, thus resulting in minimum off-target effects. The linkers used in ADC development can be classified as cleavable and non-cleavable. The former, in turn, can be grouped into three types: hydrazone, disulfide, or peptide linkers. In this review, we highlight the various linkers used in ADC development and their design strategy, release mechanisms, and future perspectives.
Identifiants
pubmed: 35214128
pii: pharmaceutics14020396
doi: 10.3390/pharmaceutics14020396
pmc: PMC8874516
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
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