Tackling solid tumour therapy with small-format drug conjugates

Author:

Deonarain Mahendra P12ORCID,Xue Quinn3

Affiliation:

1. Antikor Biopharma Ltd, Stevenage Bioscience Catalyst, Gunnels Wood Road, Stevenage, Hertfordshire SG12FX, UK

2. Department of Chemistry, Imperial College London, Exhibition Road, London SW72AZ, UK

3. Essex Biotechnology Ltd, Shun Tak Centre, Room 2818, China Merchants Tower, Connaught Road Central, Hong Kong 168-200, SAR China

Abstract

ABSTRACT The pharmacokinetic–pharmacodynamic relationship is extremely complex and tumour drug penetration is one key parameter influencing therapeutic efficacy. In the context of antibody–drug conjugates (ADCs), which has undergone many innovation cycles and witnessed many failures, this feature is being addressed by a number of alternative technologies. Immunoglobulin-based ADCs continue to dominate the industrial landscape, but smaller formats offer the promise of more-effective cytotoxic payload delivery to solid tumours, with a higher therapeutic window afforded by the more rapid clearance. To make these smaller formats viable as delivery vehicles, a number of strategies are being employed, which will be reviewed here. These include identifying the most-appropriate size to generate the larger therapeutic window, increasing the amount of functional, cytotoxic payload delivered through conjugation or half-life extending technologies or other ways of extending the dosing without inducing toxicity.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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