γδ T cell activation by bispecific antibodies.

Abstract

Bispecific antibodies have been successfully introduced into clinical application. γδ T cells are of special interest for tumor immunotherapy, due to their recognition of pyrophosphates that are overproduced by many tumor cells resulting in HLA-nonrestricted tumor cell killing. Here we describe in detail a [(Her2)2 × Vγ9] tribody construct that targets human Vγ9 T cells to HER2-expressing tumor cells. The direct comparison with other selective Vγ9 T cell agonists including phosphoantigens and nitrogen-containing bisphosphonates revealed the superiority of the [(Her2)2 × Vγ9] tribody in triggering γδ T cell-mediated tumor cell killing with negligible induction of γδ T cell death. In contrast, phosphoantigens and bisphosphonates are potent inducers of γδ T cell proliferation but less efficient enhancers of γδ T cell-mediated tumor cell killing. Collectively, our data identify unique properties of a γδ T cell-targeting [(Her2)2 × Vγ9] tribody which make it an attractive candidate for clinical application in γδ T cell-based tumor immunotherapy.

• Authors: Hans-Heinrich Oberg, Christian Kellner, Daniel Gonnermann, Matthias Peipp, Christian Peters, Susanne Sebens, Dieter Kabelitz, Daniela Wesch
• Journal: Cellular immunology (Cell Immunol) Vol. 296 Issue 1 Pg. 41-9 (Jul 2015) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 25979810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Bispecific
• Diphosphates
• Diphosphonates
• Receptors, Antigen, T-Cell, gamma-delta
• T-cell receptor Vgamma9, human
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Antibodies, Bispecific (immunology)
• CD8-Positive T-Lymphocytes (immunology, transplantation)
• Cell Line, Tumor
• Cell Proliferation
• Cytotoxicity, Immunologic
• Diphosphates (immunology)
• Diphosphonates (immunology)
• Humans
• Immunotherapy
• Lymphocyte Activation (immunology)
• Neoplasms (immunology, therapy)
• Receptor, ErbB-2 (biosynthesis, immunology)
• Receptors, Antigen, T-Cell, gamma-delta (genetics, immunology)