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TES7, a monoclonal antibody targeting B7‐H3, potently inhibits Hs‐700T growth in vivo.
Author(s) -
Liang Tony Weiyen,
Roberts Penny E,
Young Peter,
Li Pam,
Santos Mary Ann,
Chen Francine,
Mather Jennnie P,
Vehar Gordon A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.321.11
Subject(s) - monoclonal antibody , in vivo , immunohistochemistry , colorectal cancer , pancreatic cancer , staining , antibody , cancer research , pathology , biology , cancer , lung cancer , extracellular , pancreas , microbiology and biotechnology , medicine , immunology , endocrinology
Human B7‐H3, a member of the B7 family of costimulator molecules, is a ∼110kDa type I membrane protein with 4 extracellular Ig like loops (IgV1‐IgC1‐IgV2‐IgC2), a short cytoplasmic tail, and a putative isoform with only 2 extracellular Ig like loops (IgV2‐IgC2). In this report, we present and characterize TES7, a monoclonal antibody specific to human B7‐H3. We map TES7 binding to the IgV1‐IgC1 portion of B7‐H3, and demonstrate TES7/B7‐H3 interaction to be density and receptor clustering sensitive. Immunohistochemical studies of TES7 show differential staining on normal versus cancerous human tissues (normal pancreas, lung, liver, kidney, and heart were negative, membrane staining observed on colon epithelia; positive staining on 4/4 lung cancer, 4/4 colon cancer, and 6/13 pancreatic cancer samples; 4/4 breast cancer and 3/3 prostate cancers samples were positive). Using TES7 in vivo, we demonstrate growth inhibition of subcutaneously implanted Hs‐700T cells. The data presented are the first demonstration of disease‐associated reorganization of B7‐H3 surface expression, and presents TES7 as a novel tool for the study of B7‐H3 biology and as a potential cancer therapeutic.