In vitro generation of cytotoxic effectors activated by interleukin 2 (IL-2): Comparison of autologous peripheral blood stem cells (PBSC) from adults and children

Abstract

Previous studies demonstrated that ex vivo IL-2-activated PBSC could generate cytotoxic effectors without impairing haematopoietic reconstitution. Clinical experience and previous studies indicated that children with solid tumours could benefit from high-dose chemotherapy with immune modulation. We studied the generation of cytotoxic effectors from growth-factor ± chemotherapy-mobilised PBSC from 10 patients (five adults and five children) with different solid tumours. Cells were placed in culture in serum-free culture medium supplemented with IL-2 1000 U/ml ± IL-12 for 1, 2, 4 or 7 days. Anti-tumour cytotoxicity was tested against K562, Daudi and two neuroblastoma cell lines (Gau, NB91). Cultured adult PBSC in the presence of IL-2 (1000 U/ml) showed marked cytotoxicity against all the cell lines tested from day 1. At day 2, with an E:T ratio of 25:1, cytotoxicity was 53% ± 10.4, 63.2% ± 23.8, 38% ± 9.1, and 39% ± 15.7 against K562, Daudi, Gau and NB91, respectively. Cytotoxic activity of child PBSC was significantly lower (P < 0.05) and was displayed after longer culture times (day 4). No difference was found in the phenotype analysis of lymphoid subsets before and after IL-2 activation between adult and child PBSC. Haematological properties of the graft were not significantly impaired by IL-2 activation.