Nanobodies in cancer

Abstract

For treatment and diagnosis of cancer, antibodies have proven their value and now serve as a first line of therapy for certain cancers. A unique class of antibody fragments called nanobodies, derived from camelid heavy chain-only antibodies, are gaining increasing acceptance as diagnostic tools and are considered also as building blocks for chimeric antigen receptors as well as for targeted drug delivery. The small size of nanobodies (∼15 kDa), their stability, ease of manufacture and modification for diverse formats, short circulatory half-life, and high tissue penetration, coupled with excellent specificity and affinity, account for their attractiveness. Here we review applications of nanobodies in the sphere of tumor biology.

Keywords: Cancer; Diagnostics; Imaging; Nanobodies; VHH.

Figure 1. Nanobodies and their targets in relation to the tumor (microenvironment).

A. Schematic representation of a conventional human Ig, camelid HCab, and a nanobody. B. Schematic overview of the tumor-associated targets for which nanobodies have currently been established. Important targets are immune cell markers, tumor cell (membrane) proteins, receptor ligands, and proteins associated with the tumor microenvironment.

Figure 2. Overview of the applications of nanobodies in cancer diagnosis and therapy.

A. Nanobodies have been successful in diagnosis through molecular imaging techniques such as PET, SPECT, NIR, and ultrasound-based molecular imaging. B. Nanobodies can be used in a variety of tumor therapies, such as targeted radionuclide therapy, nanobody-drug conjugates, adoptive cell transfer, and vaccination.