Nanobody Conjugates for Targeted Cancer Therapy and Imaging

Abstract

Conventional antibody-based targeted cancer therapy is one of the most promising avenues of successful cancer treatment, with the potential to reduce toxic side effects to healthy cells surrounding tumor cells. However, the full potential of antibodies is severely limited due to their large size, low stability, slow clearance, and high immunogenicity. Alternatively, recently discovered nanobodies, which are the smallest naturally occurring antigen-binding format, have shown great potential for addressing these limitations. Bioconjugation of nanobodies to functional groups such as toxins, enzymes, radionucleotides, and fluorophores can improve the efficacy and potency of nanobodies, enhance their in vivo pharmacokinetics, and expand the range of potential applications. Herein, we review the superior characteristics of nanobodies in comparison to conventional antibodies and provide insight into recent developments in nanobody conjugates for targeted cancer therapy and imaging.

Delivery of Drugs into Cancer Cells Using Antibody–Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect

“…It was unknown what the endosomal escape of the cleaved PE38 was like. In the future, different formats of Ab fragments and their derivatives, such as nanobodies (approximately 15 kDa) known as single-domain Abs or variable fragments of heavy-chain (VHH) domains, will be developed in ADCs [ 62 ].…”

“…Although the Fc domain plays an important role in pharmacokinetic interactions with FcRs, IgG molecules are so large that they have problems such as membrane impermeability and their biotechnological production. Thus, nanobodies (4 nm and 2.5 nm in width and height, approximately 15 kDa) also known as VHH domains retain a specific binding ability to the corresponding antigens as Ab fragments and are expected to be a novel modality in pharmacotherapy [ 62 ]. Anti-transferrin receptor nanobodies with neurotensin, a type of ADC, was transported into the brain across the BBB via RMT [ 44 ].…”

Nanoanticuerpos: desarrollo biotecnológico y aplicaciones

“…La adaptación de los Nac a células CAR-T (del inglés Chimeric Antigen Receptor-T Cells), se han evaluado siendo parte de su receptor de reconocimiento, o como moléculas de secreción con propiedades inmunomoduladoras para optimizar su efecto antitumoral (Xie et al, 2020). De igual manera, se ha explorado su aplicación al conjugarlos con diferentes fármacos, enzimas y toxinas (Kang et al, 2021). En la Tabla II, se muestran algunos ejemplos de estos Nac.…”

Application of Nano-Antibodies for Cancer Immunotherapy

“…For these reasons, they are currently being pursued both diagnostic and therapeutic purposes [43,44]. In numerous clinical trials for various indications and different antigen targets, these nano-antibodies have been found to be safe and efficacious [45][46][47][48][49][50]. Two such nano-antibodies, caplacizumab and ozoralizumab, have been approved for marketing [51•, 52].…”