A novel antibody-like TCRγδ-Ig fusion protein exhibits antitumor activity against human ovarian carcinoma.
TCRγ9δ2(OT3) is a tumor-specific TCR with an unique complementarity-determining region 3 (CDR3) sequence, referred to as OT3, in its δ2 chain. This region was identified in tumor-infiltrating lymphocytes (TILs) from human ovarian epithelial carcinoma. We demonstrated that TCRγ9δ2(OT3)-Fc, a fusion protein composed of the complete extracellular domains of the γ9 and δ2 chains linked to the Fc domains of human IgG1, exhibited successful binding to multiple human carcinoma cell lines. In vitro, TCRγ9δ2(OT3)-Fc mediated cell killing via antibody-dependent cellular cytotoxicity (ADCC) in a dose-dependent manner. In vivo, TCRγ9δ2(OT3)-Fc significantly inhibited tumor growth and enhanced survival in human ovarian carcinoma xenograft models. Our findings suggest that the TCRγ9δ2(OT3)-Fc fusion protein possesses both the antigen-recognition properties of TCR γδ and the Fc-mediated effector functions of the antibody.
Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, National Key Laboratory of Medical Molecular Biology, Beijing, China. Electronic address: jingzheng0420@gmail.com.
Jing
J
Zheng
Yang
Y
Guo
Xu
X
Ji
Lianxian
L
Cui
Wei
W
He
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020014:K562 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015202:Protein Engineering / Q000379:methods; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D000970:Antineoplastic Agents; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011993:Recombinant Fusion Proteins
ADCC; TCR γδ; Tumor-targeted immunotherapy; Xenograft model