{"id":"doi:10.3389/fimmu.2017.01603","kind":"review","title":"Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics","authors":["Bannas P","Hambach J","Koch-Nolte F"],"author_count":3,"year":2017,"published":"2017-11-22","venue":"Frontiers in immunology","cited_by":472,"doi":"10.3389/fimmu.2017.01603","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3389/fimmu.2017.01603","archive_url":"https://space-kitty.com/papers/doi:10.3389/fimmu.2017.01603","updated":null,"pmid":"29213270","pmcid":"PMC5702627","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5702627/pdf","abstract":"Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv). scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa) and nanobody-based human heavy chain antibodies (75 kDa) can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb). Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo . Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo . Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody-based human heavy chain antibodies as antitumor therapeutics.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics\" by Bannas P, Hambach J, Koch-Nolte F, https://doi.org/10.3389/fimmu.2017.01603, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}