Chimeric univalent antibodies for treating lymphoid malignancies

Abstract

A more effective use of antibody in treating cancer appears to require derivatives with enhanced cytotoxic potential. Working with anti-idiotype antibodies directed against neoplastic lymphocytes, we have shown previously that univalent antibody derivatives with intact Fc-regions can avoid antigenic modulation while retaining the ability to recruit cytotoxic effectors such as complement. Chimeric univalent antibodies represent an extension of this approach. To prepare them Fab' gamma from antibody is linked by thioether bonds to half-cystine in normal Ig of the species to undergo immunotherapy. The derivatives FabIgG and FabFc utilize IgG and Fc gamma respectively as the effector partners of the antibody Fab' gamma. They appear superior to parent antibody in their ability to invoke complement and K-cell killing of target lymphocytes. They show promise of being minimally immunogenic and, because they present homologous Fc, should prove efficient recruiters of host effector functions.