Theranostics in immuno-oncology using nanobody derivatives

Abstract

Targeted therapy and immunotherapy have become mainstream in cancer treatment. However, only patient subsets benefit from these expensive therapies, and often responses are short‐lived or coincide with side effects. A growing modality in precision oncology is the development of theranostics, as this enables patient selection, treatment and monitoring. In this approach, labeled compounds and an imaging technology are used to diagnose patients and select the best treatment option, whereas for therapy, related compounds are used to target cancer cells or the tumor stroma. In this context, nanobodies and nanobody-directed therapeutics have gained interest. This interest stems from their high antigen specificity, small size, ease of labeling and engineering, allowing specific imaging and design of therapies targeting antigens on tumor cells, immune cells as well as proteins in the tumor environment. This review provides a comprehensive overview on the state-of-the-art regarding the use of nanobodies as theranostics, and their importance in the emerging field of personalized medicine.

Noninvasive Imaging of the Immune Checkpoint LAG-3 Using Nanobodies, from Development to Pre-Clinical Use

“…This shows that Nbs are excellent candidate molecules for the visualization of immune checkpoints within the tumor environment, like previously described in Broos et al using PD-L1 targeting Nbs [31]. Moreover, in view of repeated imaging, which could be interesting for follow up of the immune checkpoint status during therapy, it is important to note that Nbs are weakly immunogenic because of their high similarity with human variable heavy chain fragments properties (reviewed by [24]).…”

“…The use of nanobodies (Nbs), the recombinant variable domains (VHH) of heavy-chain only antibodies (HCAbs) that are naturally present in animals from the Camelidae family, is increasingly explored in the field of immuno-oncology [24]. Their small size and unique epitope targeting possibilities make them very interesting to target proteins present in dense tissues like the tumor environment [24]. Additionally, they can be easily engineered and produced in prokaryotic systems or yeast cells [25,26].…”

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

“…They are the smallest possible functional antibody derivatives that combine high affinity with improved diffusion in tumor tissues, better pharmacokinetics, and a lower immunogenicity. One of the unique characteristics of nanobodies is their ability to target antigenic epitopes at locations, which are difficult to access by large molecules, such as conventional monoclonal antibodies [97]. So far, PSMA-targeted nanobodies were developed mainly for prostate cancer imaging and were tested in preclinical studies in vitro and in mice bearing Minibodies (~80 kDa) are bivalent homodimers, with each monomer containing the variable domains scFv linked to the human IgG1 hinge and a CH3 domain (dimeric scFv-CH3) [83].…”

VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

“…In addition to the usual anti-VCAM-1 ligands (peptide and monoclonal antibody), there is a specific anti-VCAM-1 nanobody, cAbVCAM-1-5, which is composed of small fragments (2.5 nm in diameter) derived from camelid heavy chain-only antibodies. Nanobodies have already proven their utility in the field of oncology as radiotracers [119] and, therefore, constitute an interesting subject of study in atherosclerosis. Therefore, Broisat et al generated the technetium-99m-labeled anti-VCAM-1 nanobody ([ 99m Tc]Tc-cAbVCAM-1-5) recognising mouse and human homologues that successfully detect atherosclerosis by SPECT/CT imaging [111].…”