Update: affibody molecules for molecular imaging and therapy for cancer.
Affibody molecules are scaffold proteins, having a common frame of amino acids determining the overall fold or tertiary structure, but with each member characterized by a unique amino acid composition in an exposed binding surface determining binding specificity and affinity for a certain target. Affibody molecules represent a new class of affinity proteins based on a 58-amino acid residue protein domain, derived from one of the IgG binding domains of staphylococcal protein A. They combine small size ( approximately 6.5 kDa) with high affinity and specificity. Affibody molecules with nanomolar affinities were selected from an initial library (3 x 10(9) members) and, after affinity maturation, picomolar binders were obtained. The small size and simple structure of affibody molecules allow their production by chemical synthesis with homogeneous site-specific incorporation of moieties for further labeling using a wide range of labeling chemistries. The robustness and the refolding properties of affibody molecules make them amenable to labeling conditions that denature most proteins, including incubation at pH 11 at 60 degrees C for up to 60 minutes. Affibody molecules meet the requirements which are key for successful clinical use as imaging agents: high-affinity binding to the chosen target; short plasma half-life time; rapid renal clearance for nonbound drug substance and, high, continuously increasing tumor-to-organ ratios, resulting in high-contrast in vivo images shortly after injection of the diagnostic agent.
Orlova
Anna
A
Affibody AB, Bromma, Sweden. anna.orlova@bms.uu.se
Feldwisch
Joachim
J
Abrahmsén
Lars
L
Tolmachev
Vladimir
V
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D011485:Protein Binding; D011877:Radionuclide Imaging; D011878:Radiotherapy / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*
D000951:Antigens, Neoplasm; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C515865:Z(HER2.4)2 affibody; C512478:EGFR protein, human