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- W2794925559 startingPage "16" @default.
- W2794925559 abstract "Antibody–Drug Conjugates (ADCs) have been through multiple cycles of technological innovation since the concept was first practically demonstrated ~40 years ago. Current technology is focusing on large, whole immunoglobulin formats (of which there are approaching 100 in clinical development), many with site-specifically conjugated payloads numbering 2 or 4. Despite the success of trastuzumab-emtansine in breast cancer, ADCs have generally failed to have an impact in solid tumours, leading many to explore alternative, smaller formats which have better penetrating properties as well as more rapid pharmacokinetics (PK). This review describes research and development progress over the last ~10 years obtained from the primary literature or conferences covering over a dozen different smaller format-drug conjugates from 80 kDa to around 1 kDa in total size. In general, these agents are potent in vitro, particularly more recent ones incorporating ultra-potent payloads such as auristatins or maytansinoids, but this potency profile changes when testing in vivo due to the more rapid clearance. Strategies to manipulate the PK properties, whilst retaining the more effective tumour penetrating properties could at last make small-format drug conjugates viable alternative therapeutics to the more established ADCs." @default.
- W2794925559 created "2018-04-06" @default.
- W2794925559 creator A5002451877 @default.
- W2794925559 creator A5003405691 @default.
- W2794925559 creator A5037062506 @default.
- W2794925559 creator A5041454477 @default.
- W2794925559 creator A5045332430 @default.
- W2794925559 creator A5056862237 @default.
- W2794925559 creator A5085951351 @default.
- W2794925559 creator A5087428912 @default.
- W2794925559 date "2018-03-31" @default.
- W2794925559 modified "2023-10-14" @default.
- W2794925559 title "Small-Format Drug Conjugates: A Viable Alternative to ADCs for Solid Tumours?" @default.
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