Development of a bispecific monoclonal antibody against a gallium-67 chelate and the human melanoma-associated antigen p97 for potential use in pretargeted immunoscintigraphy.
A bispecific monoclonal antibody (bsmAb) has been developed against the human melanoma-associated antigen p97 and an octahedral gallium chelate (Ga-HBED) using the hybrid hybridoma technology. As tetradomas were expected to produce a maximum of ten different molecular species of immunoglobulins, the bispecific antibody was purified from this mixture by consecutive protein A affinity and cation-exchange chromatographic techniques. Although it was established by sodium dodecyl sulphate/polyacrylamide gel electrophoresis that the heavy (H) and light (L) chains of the two parental immunoglobulins were mismatched in the bispecific antibody, results from cell enzyme-linked immunosorbent assay indicated significant dual specific binding to both the melanoma cells and 67Ga-HBED. Other in vitro techniques further confirmed that the bsmAb Bi 5-56-II-17 still retained about 30%-40% simultaneous binding capacity to both the antigens, as would have been expected in a bsmAb that has ideally matched H and L chains. Preliminary in vivo experiments using nude mice bearing the human melanoma xenografts showed that the bsmAb Bi 5-56-II-17 was able to target the radioactive gallium chelate to the tumours twice as efficiently compared to the monospecific, bivalent gallium chelate antibody.
Somasundaram
C
C
Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg.
Matzku
S
S
Schuhmacher
J
J
Zöller
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000951:Antigens, Neoplasm; D005710:Gallium Radioisotopes / Q000008:administration & dosage*; D006801:Humans; D008545:Melanoma / Q000000981:diagnostic imaging*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000276:immunology*; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D005710:Gallium Radioisotopes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins