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The Journal of Immunology, 1998, 160: 3419-3426.
Copyright © 1998 by The American Association of Immunologists

A B7.1-Antibody Fusion Protein Retains Antibody Specificity and Ability to Activate Via the T Cell Costimulatory Pathway1

Pia M. Challita-Eid*, Manuel L. Penichet{ddagger}, Seung-Uon Shin{ddagger}, Tina Poles*, Nima Mosammaparast*, Kutubuddin Mahmood{dagger}, Dennis J. Slamon§, Sherie L. Morrison{ddagger} and Joseph D. Rosenblatt2,*,{dagger}

* Hematology-Oncology Unit, University of Rochester Cancer Center, and {dagger} Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642; {ddagger} 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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