A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth |
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Authors: | Merete Thune Wiiger Hege B Gehrken Øystein Fodstad Gunhild M Mælandsmo Yvonne Andersson |
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Institution: | (1) Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway;(2) University of Oslo, 0310 Oslo, Norway |
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Abstract: | Screening a phage-display single-chain antibody library for binding to the breast cancer cell line PM-1 an antibody, scFv173,
recognising activated leukocyte cell adhesion molecule (ALCAM, CD166) was isolated and its binding profile was characterized.
Positive ALCAM immunohistochemical staining of frozen human tumour sections was observed. No ALCAM staining was observed in
the majority of tested normal human tissues (nine of ten). Flow cytometry analyses revealed binding to 22 of 26 cancer cell
lines of various origins and no binding to normal blood and bone marrow cells. Antibody binding inhibited invasion of the
breast cancer cell line MDA-MB-231 by 50% in an in vitro Matrigel-coated membrane invasion assay. Reduced growth of tumours
in nude mice was observed in an in vivo model in which the mice were injected subcutaneously with colorectal carcinoma HCT
116 cells and treated with scFv173 when compared to control. In summary, we have characterized a novel fully human scFv antibody
recognising ALCAM on cancer cells and in tumour tissues that reduces cancer cell invasion and tumour growth in accordance
with the hypothesised role for ALCAM in cell growth and migration control. |
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