Emerging formats for next-generation antibody drug conjugates

Abstract

Introduction: Antibody drug conjugates now make up a significant fraction of biopharma’s oncology pipeline due to great advances in the understanding of the three key components and how they should be optimised together. With this clinical success comes innovation to produce new enabling technologies that can deliver more effective antibody-drug conjugates (ADCs) with a larger therapeutic index.

Areas covered: There are many reviews that discuss the various strategies for ADCs design but the last 5 years or so have witnessed the emergence of a number of different antibody formats compete with the standard whole immunoglobulin. Using published research, patent applications and conference disclosures, the authors review the many antibody and antibody-like formats, discussing innovations in protein engineering and how these new formats impact on the conjugation strategy and ultimately the performance. The alternative chemistries that are now available offer new linkages, stability profiles, drug:antibody ratio, pharmacokinetics and efficacy. The different sizes being considered promise to address issues, such as tumour penetration, circulatory half-life and side-effects.

Expert opinion: ADCs are at the beginning of the next stage in their evolution and as these newer formats are developed and examined in the clinic, we will discover if the predicted features have a clinical benefit. From the commercial activity, it is envisaged that smaller or fragment-based ADCs will expand oncological applications.

Keywords:

• antibody
• conjugate
• drug
• Fab
• format
• fragment
• linker
• single-chain Fv

Declaration of interest

M Deonarain and G Yahioglu are employees, co-founders and shareholders in Antikor Biopharma Ltd. Meanwhile, I Stamati and J Marklew are employees and minor shareholders in Antikor Biopharma Ltd. The authors also highlight support from Imperial College London. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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