Abstract: The present invention provides antibodies that target an E-cadherin linker segment, homologous to other segments adjacent to cell membrane in cancer cell shed proteins for diagnosis and therapy of cancers of epithelial origin. We design this peptide based in experimental observations that demonstrate shedding of E-cadherin and extracellular domains of other cell surface proteins during cancer progression and metastasis and based on our observation that a proline residue after transmembrane domain is present in many proteins on the cell surface that are targets for proteolytic processing. The corresponding antibodies were validated in vitro and in vivo using animal models and have showed no toxicity and significant tumor regression for gastric cancer, including potentiation of commercial drug, when utilized in combination.

Abstract: The present invention provides antibodies that target an E-cadherin linker segment, homologous to other segments adjacent to cell membrane in cancer cell shed proteins for diagnosis and therapy of cancers of epithelial origin. We design this peptide based in experimental observations that demonstrate shedding of E-cadherin and extracellular domains of other cell surface proteins during cancer progression and metastasis and based on our observation that a proline residue after transmembrane domain is present in many proteins on the cell surface that are targets for proteolytic processing. The corresponding antibodies were validated in vitro and in vivo using animal models and have showed no toxicity and significant tumor regression for gastric cancer, including potentiation of commercial drug, when utilized in combination.