Basic StudiesBromohydrin Pyrophosphate-stimulated Vγ9δ2 T Cells Expanded Ex Vivo From Patients With Poor-Prognosis Neuroblastoma Lyse Autologous Primary Tumor CellsChargui, Jamel*; Combaret, Valérie†; Scaglione, Virginie*; Iacono, Isabelle†; Péri, Valentine*; Valteau-Couanet, Dominique§ ∥; Dubrel, Marie∥; Angevin, Eric∥; Puisieux, Alain† ¶; Romagne, François*; Bergeron, Christophe‡Author Information *Innate Pharma, 117, Bld de Luminy, Marseille †Laboratoire de recherche translationnelle/INSERM U590, Centre Léon Bérard, rue Laënnec ‡Institut d'Hématologie-Oncologie Pédiatrique, 1 place Joseph Renaut, Lyon cedex §Département de Pédiatrie ∥Laboratoire de Recherche Translationnelle, Institut Gustave Roussy, rue Camille Desmoulins, Villejuif cedex ¶Université Claude Bernard Lyon 1, Lyon France All authors have declared there are no financial conflicts of interest in regards to this work. Supported by a grant from the Comité Départemental de l'Ain, the Comité Départemental de la Savoie and the Comité Départemental de Saône et Loire de la Ligue de Lutte Contre le Cancer. Reprints: Jamel Chargui, Innate Pharma, 117, Avenue de Luminy-BP 30191, 13276 Marseille Cedex 09 France (e-mail: email@example.com). Received for publication July 6, 2009; accepted March 9, 2010 Jamel Chargui, and Valérie Combaret the two authors contributed equally to this work. Journal of Immunotherapy: July-August 2010 - Volume 33 - Issue 6 - p 591-598 doi: 10.1097/CJI.0b013e3181dda207 Buy Metrics Abstract Gamma/delta T cells (Vγ9δ2) contribute to innate immunity and exert natural cytotoxicity against a variety of tumors. Using a synthetic phosphoantigen (Bromohydrin Pyrophosphate, BrHPP), we amplified Vγ9δ2 T cells in vitro from neuroblastoma patients. In the presence of BrHPP and low doses of IL-2, robust proliferation of Vγ9δ2 T cells was obtained from peripheral blood mononuclear cells (PBMC) harvested at diagnosis. Moderate proliferation was observed from PBMC harvested after stem cell transplantation, whereas modest levels of Vγ9δ2 T cells were obtained from PBMC harvested after induction therapy. Proliferation was observed after a single in vitro stimulation with BrHPP. After 21 days in culture, Vγ9δ2 T cells represented more than 80% of cultured cells (a 50-fold expansion from baseline). Moreover, BrHPP-amplified Vγ9δ2 T cells from patients-expressed activation markers and were able to lyse allogeneic and autologous neuroblasts. This cytotoxic activity was γδ T-cell receptor-dependent. Clinical trials using BrHPP are warranted in patients with poor-prognosis neuroblastoma, either to expand patient-derived Vγ9δ2 T cells ex vivo or by direct administration to in vivo to boost the pool of resident Vγ9δ2 T cells in vivo. © 2010 Lippincott Williams & Wilkins, Inc.