Several types of bispecific antibodies with affinity to both adenoviral coat proteins and a targeted antigen have been developed with the aim of providing the specific delivery of adenoviral gene therapy vehicle. From a phage display library of combinatorial dAb(2)s (each with all anti-adenoviral knob protein V-H fragment linked with an anti-c-Met V-H), we serendipously enriched and isolated a clone, JS5, that has polyspecificity such that it binds both the adenoviral knob protein and c-Met, despite having only one V-H domain. Our indirect observations suggest that the polyspecificity of JS5 is developed through accumalation of antibody specificity. The method of sequential immunization of a rabbit, first with the adenoviral knob protein and then with target antigens, may provide a method by which monoclonal antibodies with stand-alone polyspecificity may be developed. Such targeted polyspecific antibodies Could readily be used for redirecting adenoviral vectors to target cells. (c) 2005 Elsevier Inc. All rights reserved.