Boronated monoclonal antibody 225.28S for potential use in neutron capture therapy of malignant melanoma.
The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoclonal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity. The present report describes the conjugation of dicesium-mercapto-undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma-associated antigens (HMW-MAA), using poly-L-ornithine as a "bridge" to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron-monoclonal antibody conjugates has been studied by gel electrophoresis and ion-exchange HPLC.
Tamat
S R
SR
Department of Pharmacy, University of Sydney, Australia.
Moore
D E
DE
Patwardhan
A
A
Hersey
P
P
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D001895:Boron / Q000032:analysis / Q000627:therapeutic use*; D001896:Boron Compounds / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy; D009502:Neutrons; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001896:Boron Compounds; D001895:Boron