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Antibodies 2018, 7(2), 16;

Small-Format Drug Conjugates: A Viable Alternative to ADCs for Solid Tumours?

Antikor Biopharma Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage Herts SG12FX, UK
Department of Chemistry, Imperial College London, Exhibition Road, London SW72AZ, UK
Author to whom correspondence should be addressed.
Received: 16 February 2018 / Revised: 7 March 2018 / Accepted: 8 March 2018 / Published: 31 March 2018
(This article belongs to the Special Issue Antibody Drug Conjugates)
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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. View Full-Text
Keywords: antibody–drug conjugate; fragment; alternative scaffold; penetration; pharmacokinetics antibody–drug conjugate; fragment; alternative scaffold; penetration; pharmacokinetics

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Deonarain, M.P.; Yahioglu, G.; Stamati, I.; Pomowski, A.; Clarke, J.; Edwards, B.M.; Diez-Posada, S.; Stewart, A.C. Small-Format Drug Conjugates: A Viable Alternative to ADCs for Solid Tumours? Antibodies 2018, 7, 16.

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