Nanobody: A Small Antibody with Big Implications for Tumor Therapeutic Strategy

Abstract

The development of monoclonal antibody treatments for successful tumor-targeted therapies took several decades. However, the efficacy of antibody-based therapy is still confined and desperately needs further improvement. Nanobodies are the recombinant variable domains of heavy-chain-only antibodies, with many unique properties such as small size (~15kDa), excellent solubility, superior stability, ease of manufacture, quick clearance from blood, and deep tissue penetration, which gain increasing acceptance as therapeutical tools and are considered also as building blocks for chimeric antigen receptors as well as for targeted drug delivery. Thus, one of the promising novel developments that may address the deficiency of monoclonal antibody-based therapies is the utilization of nanobodies. This article provides readers the significant factors that the structural and biochemical properties of nanobodies and the research progress on nanobodies in the fields of tumor treatment, as well as their application prospect.

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

“…Nanocarriers are nano-sized (10–400 nm) particles that are able to encapsulate therapeutic or diagnostic molecules, which include lipid nanoparticles (liposomes), biocompatible polymers, surfactants, protein particles, RNA nanoparticles, and extracellular vesicles [ 248 , 610 , 611 , 612 , 613 , 614 , 615 , 621 , 622 ]. A variety of EGFR-targeting molecules have been utilized to effectively and selectively deliver nanocarriers to tumor stroma, including monoclonal antibodies, single-chain antibodies, nanobodies, affimers, affinity peptides, and oligonucleotide aptamers [ 623 , 624 , 625 , 626 , 627 , 628 , 629 , 630 ]. EGFR-targeting nanocarriers can deliver encapsulated drugs more efficiently via receptor-mediated endocytosis; however, escaping lysosomal degradation is a challenging issue that needs to be resolved [ 631 , 632 , 633 ].…”

CuS@BSA-NB2 Nanoparticles for HER2-Targeted Photothermal Therapy

“…Therefore, the nanobody can recognize the sites that is difficult for a conventional antibody to identify and access for the inclination of binding the concave epitopes as enzyme catalytic sites (De Genst et al, 2006). In summary, the nanobody has a huge application prospect in the treatment of tumors (Sun et al, 2021).…”

Nanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells

“…nanobodies, also known as the variable domain of the heavy chain of heavy chain antibody (VHH), were first found in dromedaries by Hamers Castermans in 1993 and then identified in Camelidae and sharks. nanobodies belong to the variable region of the heavy chain antibodies (HcAbs), which only contain variable regions of heavy chain and CH2, and CH3 but are devoid of light chain and CH1 [ 24 , 25 ]. Compared with mAbs that need six complementarity-determining regions (CDRs) to bind antigens, nanobodies only need three CDRs, and the affinity and specificity are similar [ 26 ].…”