Exploiting Innate γδ T Lymphocytes for Tumor Immunotherapy

Abstract

γδ T cells have several innate cell-like features that allow their early activation following recognition of conserved stress-induced ligands. Vγ9Vδ2 T cells, the dominant subset of γδ T cell in human peripheral blood, recognize phosphoantigens such as isopentenyl pyrophosphate generated in the mevalonate pathway. Upon activation, γδ cells display strong cytotoxicity towards various hemopoietic and nonhemopoietic tumors. Synthetic compounds have been recently patented which efficiently activate γδ cells in vitro and in vivo. In addition, the mevalonate pathway in mammalian cells can be manipulated by drugs such as aminobisphosphonates, giving rise to the development of new strategies in tumor immunotherapy. Thus, the recent developments in the discoveries of new molecules capable of activating these subsets of innate-like lymphocytes open new avenues for T cell based immunotherapy of tumors. Keywords: Vγ9Vδ2 T cells, NKT cells, tumor immunotherapy, cytokines, cytotoxicity, Innate T Lymphocytes, phosphoantigens, isopentenyl pyrophosphate, human peripheral blood, mevalonate pathway, nonhemopoietic tumors, aminobisphosphonates, T cell, T cell receptor, TNF, IFN, UL-16-binding proteins, MHC class I, stimulatory natural killer, NKG2D, ATPase, Phosphostim, Zoledro-nate, osteo-porosis, farnesyl pyrophosphate synthase, hydroxy-methylglutaryl-CoA, immune responses, interleukin, (IL)-2, lymphoma, Hematologic Malignancies, non-Hodgkin lymphoma, Patent US2010222306, WO2006103568, US2008207568, US7683045, MX2007011720, US7745422, US2006079487, US7358361, WO2006039721, WO2009056952, US2007134273, Patent US2006246520, WO2008146167, US2010189681, EP2150258, AT459360, EP1426052, US2010254940, US2006194755, JP2006510629, US2010009447, US7749760, JP2010017134, US2009304688, EP1878440, JP2009544582, WO2008006895, EP2040750