Compositions and methods for rendering tumor cells susceptible to CD8+ T cell-mediated killing

摘要

The present invention provides an immunoconjugate having the formula: T-c-En-c-Fcn or T-c-Fcn-c-En; wherein, T is a single chain variable portion fragment of a monoclonal antibody (scFv) directed to a target protein, polypeptide, or fragment thereof, which is highly expressed on cancer cells; E is two or more foreign immunogenic CD8+ T cell antigenic epitopes; c is a peptide or polypeptide fragment thereof, capable of being cleaved by a specific protease; and Fc is two or more Fc portions of an IgG antibody. Nucleic acid sequences encoding the same and vectors containing said nucleic acid sequences are also provided. Methods of making the immunoconjugate, along with methods of making target cells susceptible to CTL mediated cell killing, and methods for treatment of cancers are also provided.

主权项

1. An immunoconjugate having the formula:
T-c-Fcn-c-En; wherein T is a single chain variable portion fragment of a monoclonal antibody (scFv) directed to a target protein, polypeptide, or fragment thereof, which is highly expressed on cancer cells, and selected from the group consisting of scFv directed to mesothelin, epidermal growth factor receptor (EGFR), NKG2D, or Her2/neu protein; En is two or more foreign immunogenic CD8+ T cell antigenic epitopes derived from ovalbumin, Epstein-Barr virus, cytomegalovirus, human papilloma virus, and influenza wherein n is 1 to 10; c is a peptide or polypeptide fragment thereof, capable of being cleaved by by furin, MMP1 or MMP9; and Fcn is two or more Fc portions of an IgG antibody wherein n is 1 to 10.