Monoclonal antibodies (mAbs) are large and have limitations as
cancer therapeutics. Human single-chain variable fragment (scFv) is a small antibody as a good alternative. It can easily enter
cancer tissues, has no immunogenicity and can be produced in bacteria to decrease the cost. The
chemokine receptor CXCR4 is overexpressed in different
cancer cells. It plays an important role in
tumor growth and
metastasis. Its overexpression is associated with poor prognosis in
cancer patients and is regarded as an attractive target for
cancer treatment. In this study, a
peptide on the CXCR4 extracellular loop 2 (ECL2) was used as an
antigen for screening a human scFv antibody library by yeast two-hybrid method. Three anti-CXCR4
scFv antibodies were isolated. They could bind to CXCR4
protein and three
cancer cell lines (DU145, PC3, and MDA-MB-231) and not to 293T and 3T3 cells as negative controls. These three scFvs could decrease the proliferation, migration, and invasion of these
cancer cells and promote their apoptosis. The two scFvs were further examined in a mouse xenograft model, and they inhibited the
tumor growth.
Tumor immunohistochemistry also demonstrated that the two scFvs decreased
cancer cell proliferation and
tumor angiogenesis and increased their apoptosis. These results show that these anti-CXCR4 scFvs can decrease
cancer cell proliferation and inhibit
tumor growth in mice, and may provide
therapy for various
cancers.