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 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.
Challita-Eid
P M
PM
Hematology-Oncology Unit, University of Rochester Cancer Center, NY 14642, USA.
Penichet
M L
ML
Shin
S U
SU
Poles
T
T
Mosammaparast
N
N
Mahmood
K
K
Slamon
D J
DJ
Morrison
S L
SL
Rosenblatt
J D
JD
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity / Q000235:genetics*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics; D016466:CHO Cells; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology; D006224:Cricetinae; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000138:chemical synthesis / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D007074:Immunoglobulin G; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins