A novel antibody-like TCRγδ-Ig fusion protein exhibits antitumor activity against human ovarian carcinoma

TCR gamma 9 delta 2(OT3) is a tumor-specific TCR with an unique complementarity-determining region 3 (CDR3) sequence, referred to as OT3, in its delta 2 chain. This region was identified in tumor-infiltrating lymphocytes (TILs) from human ovarian epithelial carcinoma. We demonstrated that TCR gamma 9 delta 2(OT3)-Fc, a fusion protein composed of the complete extracellular domains of the gamma 9 and delta 2 chains linked to the Fc domains of human IgG1, exhibited successful binding to multiple human carcinoma cell lines. In vitro, TCR gamma 9 delta 2(OT3)-Fc mediated cell killing via antibody-dependent cellular cytotoxicity (ADCC) in a dose-dependent manner. In vivo, TCR gamma 9 delta 2(OT3)-Fc significantly inhibited tumor growth and enhanced survival in human ovarian carcinoma xenograft models. Our findings suggest that the TCR gamma 9 delta 2(OT3)-Fc fusion protein possesses both the antigen-recognition properties of TCR gamma delta and the Fc-mediated effector functions of the antibody. (C) 2013 Published by Elsevier Ireland Ltd.