Anti-tumour activity of aminopterin-monoclonal antibody conjugates; in vitro and in vivo comparison with methotrexate-monoclonal antibody conjugates.

Abstract

Two related folate antagonists aminopterin (AMN) and methotrexate (MTX) were used to produce drug-antibody conjugates and their tumouricidal effects compared in vitro and in vivo. Active ester derivatives were produced with the use of N-hydroxysuccinimide (NHS) and covalently coupled to monoclonal antibodies (MoAb) reactive with murine cell surface antigens; approximately 11 molecules of AMN or 13 molecules of MTX were specifically bound per molecule of anti-Ly-2.1, with good retention of antibody activity and protein recovery. AMN was a more effective inhibitor of tumour cell growth in vitro than MTX, and AMN-anti-Ly-2.1 conjugates were also more potent in vitro than MTX-anti-Ly-2.1 conjuga..