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 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 tum...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-04, Vol.160 (7), p.3419-3426
Main Authors: Challita-Eid, Pia M, Penichet, Manuel L, Shin, Seung-Uon, Poles, Tina, Mosammaparast, Nima, Mahmood, Kutubuddin, Slamon, Dennis J, Morrison, Sherie L, Rosenblatt, Joseph D
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibody Specificity - genetics
B7-1 Antigen - genetics
B7-1 Antigen - immunology
B7-1 Antigen - metabolism
Base Sequence
Binding Sites, Antibody - genetics
Cell Membrane - genetics
Cell Membrane - immunology
CHO Cells
Cricetinae
Humans
Immunoglobulin G - biosynthesis
Immunoglobulin G - genetics
Immunoglobulin G - physiology
Lymphocyte Activation - genetics
Lymphocyte Activation - immunology
Molecular Sequence Data
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - immunology
Recombinant Fusion Proteins - biosynthesis
Recombinant Fusion Proteins - chemical synthesis
Recombinant Fusion Proteins - immunology
Recombinant Fusion Proteins - physiology
T-Lymphocytes - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.7.3419