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  • A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells.

A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of Vγ9Vδ2-T cells.

Oncoimmunology (2018-01-04)
Renée C G de Bruin, John P Veluchamy, Sinéad M Lougheed, Famke L Schneiders, Silvia Lopez-Lastra, Roeland Lameris, Anita G Stam, Zsolt Sebestyen, Jürgen Kuball, Carla F M Molthoff, Erik Hooijberg, Rob C Roovers, James P Di Santo, Paul M P van Bergen En Henegouwen, Henk M W Verheul, Tanja D de Gruijl, Hans J van der Vliet
ABSTRACT

Though Vγ9Vδ2-T cells constitute only a small fraction of the total T cell population in human peripheral blood, they play a vital role in tumor defense and are therefore of major interest to explore for cancer immunotherapy. Vγ9Vδ2-T cell-based cancer immunotherapeutic approaches developed so far have been generally well tolerated and were able to induce significant clinical responses. However, overall results were inconsistent, possibly due to the fact that these strategies induced systemic activation of Vγ9Vδ2-T cells without preferential accumulation and targeted activation in the tumor. Here we show that a novel bispecific nanobody-based construct targeting both Vγ9Vδ2-T cells and EGFR induced potent Vγ9Vδ2-T cell activation and subsequent tumor cell lysis both in vitro and in an in vivo mouse xenograft model. Tumor cell lysis was independent of KRAS and BRAF tumor mutation status and common Vγ9Vδ2-T cell receptor sequence variations. In combination with the conserved monomorphic nature of the Vγ9Vδ2-TCR and the facile replacement of the tumor-specific nanobody, this immunotherapeutic approach can be applied to a large group of cancer patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
5(6)-Carboxyfluorescein diacetate N-succinimidyl ester, BioReagent, suitable for fluorescence, ≥90% (HPLC)
Sigma-Aldrich
Anti-Myc Tag Antibody, clone 4A6, clone 4A6, Upstate®, from mouse