title: Emerging formats for next-generation antibody drug conjugates.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Antikor Biopharma Ltd, Stevenage Bioscience Catalyst , Gunnels Wood Road, Stevenage, Herts, SG1 2FX , UK.
authors: Mahendra P
authors: MP
authors: Deonarain
authors: Gokhan
authors: G
authors: Yahioglu
authors: Ioanna
authors: I
authors: Stamati
authors: Jared
authors: J
authors: Marklew
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D015202:Protein Engineering / Q000379:methods
chemical_list: D000906:Antibodies; D018796:Immunoconjugates
keywords: Fab; antibody; conjugate; drug; format; fragment; linker; single-chain Fv