Killing of human tumor cells by antibody C3b conjugates and human complement.
To potentiate the lytic action of complement on tumor cells, we have constructed heteroconjugates composed of monoclonal antibody and of the human C3b component of complement. The conjugates were formed efficiently using the heterobifunctional cross-linking reagent SPDP. The monoclonal antibody-C3b conjugate promoted the killing of K562 tumor cells by normal human serum. Treatment of the tumor cells with the monoclonal antibody and normal human serum resulted in 10-15% lysis. However, following pretreatment of the cells with antibody-C3b conjugates, their lysis by normal human serum increased to 70%. The conjugate activated selectively the alternative pathway of complement and the C3b component in the conjugate was highly resistant to cleavage and inactivation by the complement regulatory proteins Factors H and I. These results suggest that the coupling of C3b molecules to monoclonal antibodies anti-unique tumor antigens produces a potent complement-activating reagent which may act specifically on tumor cells and promote cancer therapy.
Reiter
Y
Y
Weizmann Institute of Science, Rehovot, Israel.
Fishelson
Z
Z
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016923:Cell Death / Q000276:immunology; D003179:Complement C3b / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000627:therapeutic use*; D003432:Cross-Linking Reagents; D003601:Cytotoxicity Tests, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D005976:Glutaral; D006801:Humans; D007122:Immunoelectrophoresis; D009369:Neoplasms / Q000628:therapy*; D013388:Succinimides; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D013388:Succinimides; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; D003179:Complement C3b; D003165:Complement System Proteins; D005976:Glutaral