Modifying interleukin-2 concentrations during culture improves function of T cells for adoptive immunotherapy

BackgroundAdoptive immunotherapy with cytotoxic T cells has shown promising clinical results in patients with metastatic melanoma and post-transplant-associated viral infections. Cell transfer therapies often require the ex vivo expansion of large numbers of reactive lymphocytes. Therefore interleukin-2 (IL-2), a potent T-cell mitogenic cytokine that critically affects the features and effectiveness of T cells, is frequently added to cell culture media.MethodsWe examined the influence of various IL-2 concentrations on cell growth, cytotoxicity, cytokine release and surface marker expression of tumor-infiltrating lymphocytes (TIL) during a standard 14-day rapid expansion phase. The study was conducted under good manufacturing practice (GMP) conditions, using approved reagents in a class 10000 laboratory.ResultsT-cell cultures grown in very high IL-2 concentrations (600–6000 IU/mL) expanded massively and maximally secreted interferon (IFN)-γ in response to antigenic stimulation, but exhibited only low direc...