Bromohydrin pyrophosphate-stimulated Vgamma9delta2 T cells expanded ex vivo from patients with poor-prognosis neuroblastoma lyse autologous primary tumor cells.

Abstract

Gamma/delta T cells (Vgamma9delta2) contribute to innate immunity and exert natural cytotoxicity against a variety of tumors. Using a synthetic phosphoantigen (Bromohydrin Pyrophosphate, BrHPP), we amplified Vgamma9delta2 T cells in vitro from neuroblastoma patients. In the presence of BrHPP and low doses of IL-2, robust proliferation of Vgamma9delta2 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 Vgamma9delta2 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, Vgamma9delta2 T cells represented more than 80% of cultured cells (a 50-fold expansion from baseline). Moreover, BrHPP-amplified Vgamma9delta2 T cells from patients-expressed activation markers and were able to lyse allogeneic and autologous neuroblasts. This cytotoxic activity was gammadelta T-cell receptor-dependent. Clinical trials using BrHPP are warranted in patients with poor-prognosis neuroblastoma, either to expand patient-derived Vgamma9delta2 T cells ex vivo or by direct administration to in vivo to boost the pool of resident Vgamma9delta2 T cells in vivo.

• Authors: Jamel Chargui, Valérie Combaret, Virginie Scaglione, Isabelle Iacono, Valentine Péri, Dominique Valteau-Couanet, Marie Dubrel, Eric Angevin, Alain Puisieux, François Romagne, Christophe Bergeron
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2010 Jul-Aug Vol. 33 Issue 6 Pg. 591-8 ISSN: 1537-4513 [Electronic] United States
• PMID: 20551838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Cytokines
• Diphosphates
• Receptors, Antigen, T-Cell, gamma-delta
• T-cell receptor Vdelta2, human
• T-cell receptor Vgamma9, human
• bromohydrin pyrophosphate

Topics

• Antigens, Neoplasm (immunology)
• Cancer Vaccines
• Cell Line, Tumor
• Cell Proliferation
• Cytokines (metabolism)
• Cytotoxicity, Immunologic
• Diphosphates (immunology)
• Disease Progression
• Humans
• Lymphocyte Activation
• Neoplasm Staging
• Neuroblastoma (immunology, pathology, physiopathology)
• Prognosis
• Receptors, Antigen, T-Cell, gamma-delta (metabolism)
• T-Lymphocytes (immunology, metabolism, pathology)