Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments. gamma delta T cells, which have major histocompatibility complex (MHC)-unrestricted lytic activity, have become a promising candidate population for adoptive cell transfer therapy. We previously established a stable condition for expanding gamma delta T cells by using anti-gamma delta T-cell receptor (TCR) antibody. In this study, we found that adoptive transfer of the expanded gamma delta T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status. We further investigated the characteristics of these antibody-expanded gamma delta T cells compared to the more commonly used phosphoantigen-expanded gamma delta T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies. Slow but sustained proliferation of human peripheral blood gamma delta T cells was observed upon stimulation with anti-gamma delta TCR antibody. Compared to phosphoantigen-stimulated gamma delta T cells, the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines. It is noteworthy that the anti-gamma delta TCR antibody could expand both the V delta 1 and V delta 2 subsets of gamma delta T cells. The in vitro-expanded V delta 1 T cells displayed comparable tumour cell-killing activity to V delta 2 T cells. Importantly, owing to higher C-C chemokine receptor 4 (CCR4) and CCR8 expression, the V delta 1 T cells were more prone to infiltrate CCL17-or CCL22-expressing lymphomas than the V delta 2 T cells. Characterizing the peripheral blood gamma delta T cells from lymphoma patients further confirmed that the anti-gamma delta TCR antibody-expanded gamma delta T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded gamma delta T cells. Cellular & Molecular Immunology (2012) 9, 34-44; doi: 10.1038/cmi.2011.16; published online 13 June 2011