Antibody-drug conjugates as targeted therapies: Are we there yet? A critical review of the current clinical landscape.

ADC Antibody-drug conjugate Exposure-response PK Pharmacokinetics Prodrug Slow-release Targeted drug delivery

Journal

Drug discovery today. Technologies
ISSN: 1740-6749
Titre abrégé: Drug Discov Today Technol
Pays: England
ID NLM: 101235076

Informations de publication

Date de publication:
Dec 2020
Historique:
received: 29 06 2020
accepted: 15 07 2020
entrez: 13 12 2021
pubmed: 14 12 2021
medline: 15 12 2021
Statut: ppublish

Résumé

Antibody-drug conjugates (ADCs) are targeted therapies with the expectation of broadened therapeutic window due to tumor-specific drug delivery. Recent approvals, including ADCs with a novel payload class, topoisomerase-1 inhibitors, generated renewed excitement in the field. We provide a critical review of approved and late-stage molecules, discuss strategies in solid tumors and ADCs outside oncology. Our pharmacokinetics-based assessment of targeting suggests that ADCs, especially in solid tumors, rely on additional mechanisms for efficacy including slow-release of the payload to the circulation at potentially efficacious levels. Further adjustments in the technology are needed to fulfill the promise of true targeted drug delivery.

Identifiants

pubmed: 34895651
pii: S1740-6749(20)30007-X
doi: 10.1016/j.ddtec.2020.07.002
pii:
doi:

Substances chimiques

Immunoconjugates 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

13-22

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Edit Tarcsa (E)

AbbVie Bioresearch Center, 100 Research Dr., Worcester, MA, 01605, USA. Electronic address: edit.tarcsa@abbvie.com.

Magali R Guffroy (MR)

AbbVie Inc., 1 North Waukegan Rd, North Chicago, IL, 60064, USA.

Hadi Falahatpisheh (H)

AbbVie South San Francisco, CA, 94080, USA.

Colin Phipps (C)

AbbVie Inc., 1 North Waukegan Rd, North Chicago, IL, 60064, USA.

John C Kalvass (JC)

AbbVie Inc., 1 North Waukegan Rd, North Chicago, IL, 60064, USA.

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Classifications MeSH