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.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Oberg HH,Kellner C,Gonnermann D,Peipp M,Peters C,Sebens S,Kabelitz D,Wesch D

doi

10.1016/j.cellimm.2015.04.009

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

41-9

issue

1

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(15)00095-7

journal_volume

296

pub_type

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