Polymer-antibody fragment conjugates for biomedical applications

Many proteins benefit from improved solubility, immunocompatibility, pharmacokinetics or stability upon conjugation to polymers. For protein-conjugates used in delivery or imaging in vivo, this can mean increased efficacies due to longer circulatory half-lives or increased intracellular stability. In vitro, conjugation to polymers can increase stability, reduce aggregation, or mediate multimerization or phase separation of proteins to increase assay sensitivities or improve signal detection. The emergence of recombinant antibody technologies over the past two decades has allowed relatively simple isolation in vitro of (human) antibody fragments, such as Fabs and single chain variable fragments (scFvs), that retain the binding properties of their parent molecules and may exhibit additional properties such as reduced immunogenicity, improved tissue penetration or increased packing density on sensor surfaces due to their small sizes. In addition, protein engineering approaches that facilitate their chemical functionalization have seen antibody fragments linked to a broad spectrum of chemically and functionally diverse polymeric molecules. Of the varied strategies used in polymer-protein coupling, amine and cysteine conjugation are the most widely applied chemistries with antibody fragments. Simple conjugation to poly(ethyleneglycol) can increase half-life, decrease renal clearance, improve stability and reduce aggregation of antibody fragments without compromising their antigen binding. Meanwhile, engineering of antibody fragments can be used to control conjugation to polymers and coupling to responsive polymers can enable intracellular delivery or context responsive release of a drug payload from a polymer-antibody fragment complex. Recent years have seen polymer-antibody fragment conjugates increasingly encroach into areas traditionally associated with monoclonal antibody-polymers and we discuss the potential of such conjugates, in vivo and in vitro, in applications such as drug delivery, tissue engineering, diagnostics and bioseparation.