A single exercise bout augments the ex vivo expansion and anti-tumor activity of Vdelta2 T-cells: Implications for allogeneic adoptive transfer immunotherapy

Abstract

Gamma-delta T-Cells are emerging candidates for allogeneic (donor to patient) adoptive transfer immunotherapy to treat both solid and ‘liquid’ tumors. However, the numbers of γ - δ T-cell in blood are relatively low and new, cost effective methods are sought to facilitate their mobilization and ex vivo expansion from healthy donors. The aim of this study was to determine if a single exercise bout would augment the ex vivo expansion and function of γ - δ T-cells using a clinical grade protocol designed to preferentially expand the Vdelta2 subtype. Peripheral blood mononuclear cells (PBMCs) isolated from healthy donors (n = 12) before and immediately after 30-min of steady state cycling exercise were expanded with zoledronic acid and IL-2 for 14 days. Exercise doubled the rate of γ - δ T-cell expansion, even after adjusting for pre-expansion gamma-delta T-cells numbers. Exercise did not affect γ - δ T-cell phenotypic shifts following expansion. Using a series of standard allogeneic tumor target cells in a 4 h cytotoxicity assay, γ - δ T-cells expanded after exercise were better at killing target cells of leukemia (K562), lymphoma (721.221) and multiple myeloma origin (U266) (increase: 1.5-fold compared to pre-exercise). We conclude that a single exercise bout in healthy donors markedly augments the ex vivo expansion and anti-tumor activity of gamma-delta T-cells. Exercising donors prior to blood donation for adoptive T-cell therapy may elicit better clinical outcomes in cancer patients after transplant.