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*
Hematology-Oncology Unit, University of Rochester Cancer Center, and
Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642;
Department of Microbiology and Molecular Genetics, Molecular Biology Institute, and
§
Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, CA 90095; and
¶
Institute of Environment and Life Science, Hallym University, Kangwon-Do, Korea
We describe the construction and characterization of an Ab fusion protein specific for the tumor-associated Ag HER2/neu linked to sequences encoding the extracellular domain of the B7.1 T cell costimulatory ligand. The Ab domain of the fusion molecule will specifically target HER2/neu-expressing tumor cells, while the B7.1 domain is designed to activate a specific immune response. We show that the B7.1 fusion Ab retained ability to selectively bind to the HER2/neu Ag and to the CTLA4/CD28 counter-receptors for B7.1. Specific T cell activation was observed when the B7.1 Ab fusion protein was bound to HER2/neu-expressing cells. The use of the B7.1 Ab fusion protein may overcome limitations of gene transfer and/or standard Ab therapy and represents a novel approach to the eradication of minimal residual disease.
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