Therapeutic potential of monoclonal antibodies to the leukocyte-common antigen. Synergy and interference in complement-mediated lysis.

A series of rat monoclonal antibodies against the human leukocyte-common antigen were isolated and, by means of competitive binding assays with purified antigen, two distinct groups were defined that recognize different epitopes of the molecule. None of these antibodies were lytic with human complement, but when antibodies against each of these two epitopes were used in combination, synergistic lysis with human complement could be obtained. Synergistic lysis was only seen when each antibody of the pair was of the IgG2b subclass. IgG2a antibodies could not synergize, and in fact could interfere with lysis obtained by the pair of IgG2b antibodies. Although synergy has so far only been studied for rat monoclonal antibodies we also show that it is possible with mouse antibodies or with combinations of mouse and rat antibodies. The information about the principles of synergy and its interference should provide a rationale for using well-planned cocktails of monoclonal antibodies for therapy rather than a shotgun polyclonal antiserum.