PRODUCTION, BINDING AND CYTOTOXICITY OF HUMAN MOUSE CHIMERIC MONOCLONAL ANTIBODY-NEOCARZINOSTATIN CONJUGATE

A human/mouse chimeric Fab monoclonal antibody A7 (chFabA7) was covale ntly coupled to neocarzinostatin (NCS) by the SPDP method at various c hFabA7:NCS substitution ratios. The antigen-binding activity of the co njugate, examined by ELISA using fixed antigen-positive colon cancer c ells, was identical to that of the parent chFabA7 when one mole of NCS was conjugated, but was reduced with 2 or 3 moles of conjugated NCS. By means of a colony-forming assay, the cytocidal effect of the conjug ate on antigen-positive cancer cells was found to be stronger than tha t of free NCS, whereas in antigen-negative cancer cells it was similar to that of free NCS. This effect was attenuated by adding an excess a mount of monoclonal antibody A7. These findings indicate that the conj ugate has an antigen-specific cytocidal action, and thus chFabA7-NCS i s a promising tool for targeting cancer chemotherapy.