A review of current status and future perspectives for novel biotherapeutics
By William Chin, PhD, Project Manager, EUCRAF
A review paper entitled "Beyond peptides and mAbs—current status and future perspectives for biotherapeutics with novel constructs" was recently published in the March 2015 issue of the Journal of Clinical Pharmacology by AlDeghaither D et al. The authors have reviewed the currently FDA approved antibodies for the treatment of cancer and compared its various pharmacologic properties as well as highlighting other biotherapeutics using novel constructs. Below is a summary of the content of the review paper:
- Unconjugated monoclonal antibody therapy - A short overview of monoclonal antibodies and how advanced technologies are used to manipulate mAb structural properties to modify immunogenicity, size, afﬁnity for target antigen and customization of other antibody properties to modulate the immune system and alteration of cancer-related signaling. The examples of mAb structural manipulation include Fab and Fc domain modiﬁcations.
- Immunoconjugates - Examples of various immunoconjugates such as the antibody-drug conjugates (ADC), immunotoxins, immunocytokine conjugates (ICs) and radioimmunoconjugates were elaborated.
- Ig-like scaffolds - The advancement of scientific understanding of the immunoglobulin molecule has led to the discovery and development of recombinant antibody fragments such nanobodies, domain antibodies (dAbs), and bispeciﬁc scaffolds such as Bispeciﬁc T cellEngager (BiTE), Dual Afﬁnity ReTargeting (DART), tetravalent tandem antibodies (TandAbs) and antibody-peptide fusion.
- Peptides - An overview of the various peptides was provided by the authors. These include peptide hormones, luteinizing hormone-releasing hormone (LHRH) agonists and antagonists, somatostatin analogs, peptide vaccines, homing peptides, cell penetrating peptides (CPPs) and peptide-based drugs.
- Non-Ig-based protein scaffolds - These are novel structures designed as derivatives of naturally occurring substrates or protein. They include anticalins, adnectins, designed ankyrin repeat proteins (DARPins) and avimers.
The authors concluded that the next frontier in protein and peptide therapeutics will be the development of internalizing antibodies and peptides that can target cell cytoplasm and other speciﬁc subcellular compartments to either manipulate intracellular processes or deliver toxic drugs to cause targeted cell death.
1. J Clin Pharmacol. 2015 Mar;55 Suppl 3:S4-S20. Beyond peptides and mAbs-current status and future perspectives for biotherapeutics with novel constructs. AlDeghaither D, Smaglo BG, Weiner LM.