A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth.
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.
Wiiger
Merete Thune
MT
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. merete.thune.wiiger@rr-research.no
Gehrken
Hege B
HB
Fodstad
Øystein
Ø
Maelandsmo
Gunhild M
GM
Andersson
Yvonne
Y
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000276:immunology*; D000818:Animals; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000627:therapeutic use*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D057127:Single-Chain Antibodies / Q000627:therapeutic use*; D015996:Survival Rate
D020410:Activated-Leukocyte Cell Adhesion Molecule; D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies