Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design.
High-precision tumor targeting with conventional therapeutics is based on the concept of the ideal drug as a "magic bullet"; this became possible after techniques were developed for production of monoclonal antibodies (mAbs). Innovative DNA technologies have revolutionized this area and enhanced clinical efficiency of mAbs. The experience of applying small-size recombinant antibodies (monovalent binding fragments and their derivatives) to cancer targeting showed that even high-affinity monovalent interactions provide fast blood clearance but only modest retention time on the target antigen. Conversion of recombinant antibodies into multivalent format increases their functional affinity, decreases dissociation rates for cell-surface and optimizes biodistribution. In addition, it allows the creation of bispecific antibody molecules that can target two different antigens simultaneously and do not exist in nature. Different multimerization strategies used now in antibody engineering make it possible to optimize biodistribution and tumor targeting of recombinant antibody constructs for cancer diagnostics and therapy.
Deyev
Sergey M
SM
Russian Academy of Sciences, Shemyakin/Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation. deyev@ibch.ru
Lebedenko
Ekaterina N
EN
D018033:Antibodies, Bispecific / Q000235:genetics / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism*; D000915:Antibody Affinity; D000951:Antigens, Neoplasm / Q000276:immunology; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D011487:Protein Conformation; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins