Improving the targeting of therapeutics with single-domain antibodies

ABSTRACT

Introduction: The targeted delivery of therapeutic agents greatly increases their effectiveness while simultaneously reducing negative side effects. In the past, targeting of therapeutics has been accomplished with nucleic acids, peptides/proteins, and conventional antibodies. A promising alternative to the conventional antibodies often used in therapeutic targeting are significantly smaller-sized antibody fragments known as single-domain antibodies (sdAbs).

Areas Covered: Recent advances in the utility of sdAbs for targeting of therapeutic agents along with relevant examples from the literature are discussed. Their advantages when compared to other targeting strategies as well as their challenges and limitations is also covered.

Expert Opinion: The development of sdAb-based targeted therapeutics will likely continue. The identification of novel protein modification techniques will provide more options for sdAb modification (conjugation, immobilization, functionalization), allowing a wider array of therapeutic agents to be successfully targeted and delivered using sdAbs. This will also spur the selection of sdAbs with specificity for other targets having relevance towards therapeutics.

KEYWORDS:

• single-domain antibodies (sdAb)
• bioconjugation
• targeted delivery
• nanoparticle
• antibody drug conjugate (ADC)

Article highlights

• The article highlights the potential benefits of single-domain antibodies (sdAbs) as tools for the targeted delivery of therapeutic agents.

• The authors review current research efforts that utilize sdAbs for the target delivery of a range of therapeutic agents.

• The authors provide a detailed comparison of conventional antibodies and sdAbs, highlighting both advantages and limitations to the recombinant antibody structures.

• The authors discuss the current limitations encountered with advancing sdAbs to the clinical trials and the efforts to circumvent these obstacles.

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Declaration of interest

Funding was received from Naval Research Laboratory Office of Naval Research Defense Threat Reduction Agency. 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