The present disclosure relates to the generation of an antibody that specifically recognizes and binds Endosialin, a cell surface antigen characteristic of tumor pericytes and cells of tumor stroma. The antibody has the ability to become internalized in Endosialin expressing cells and to block the activation of MAPK in PDGF stimulated human pericytes. The antibody is able to block angiogenesis induced by LGALS3BP, a known Endosialin interactor and to inhibit tumor growth alone and in combination with 1959, a humanized antibody against LGALS3BP in human osteosarcoma xenograft. Furthermore, upon conjugation of the humanized version of the anti-Endosialin antibody with a duocarmycin derivative, the resulting ADC displays potent and antigen dependent in vitro tumor cell cytotoxicity and effective antitumor efficacy in vivo. The disclosure is also related to nucleotides encoding the antibodies of the disclosure and cell expressing the antibodies.

Endosialin-binding antibody

Gianluca Sala;Emily CAPONE
2017

Abstract

The present disclosure relates to the generation of an antibody that specifically recognizes and binds Endosialin, a cell surface antigen characteristic of tumor pericytes and cells of tumor stroma. The antibody has the ability to become internalized in Endosialin expressing cells and to block the activation of MAPK in PDGF stimulated human pericytes. The antibody is able to block angiogenesis induced by LGALS3BP, a known Endosialin interactor and to inhibit tumor growth alone and in combination with 1959, a humanized antibody against LGALS3BP in human osteosarcoma xenograft. Furthermore, upon conjugation of the humanized version of the anti-Endosialin antibody with a duocarmycin derivative, the resulting ADC displays potent and antigen dependent in vitro tumor cell cytotoxicity and effective antitumor efficacy in vivo. The disclosure is also related to nucleotides encoding the antibodies of the disclosure and cell expressing the antibodies.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/762373
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