A B7.1-ANTIBODY FUSION PROTEIN RETAINS ANTIBODY SPECIFICITY AND ABILITY TO ACTIVATE VIA THE T-CELL COSTIMULATORY PATHWAY

We describe the construction and characterization of an Ab fusion prot ein specific for the tumor-associated Ag HER2/neu linked to sequences encoding the extracellular domain of the B7.1 T cell costimulatory lig and, The Ab domain of the fusion molecule will specifically target HER 2/neu-expressing tumor cells, while the B7.1 domain is designed to act ivate a specific immune response, We show that the B7.1 fusion Ab reta ined ability to selectively bind to the HER2/neu Ag and to the CTLA4/C D28 counter-receptors for B7.1, Specific T cell activation was observe d when the B7.1 Ab fusion protein was bound to HER2/neu-expressing cel ls, The use of the B7.1 Ab fusion protein may overcome limitations of gene transfer and/or standard Ab therapy and represents a novel approa ch to the eradication of minimal residual disease.