TY - JOUR
T1 - In vitro generation of cytotoxic effectors activated by interleukin 2 (IL-2)
T2 - Comparison of autologous peripheral blood stem cells (PBSC) from adults and children
AU - Valteau-Couanet, D.
AU - Angevin, E.
AU - Leboulaire, C.
AU - Beaussier, P. S.
AU - Bayle, C.
AU - Hartmann, O.
AU - Beaujean, F.
PY - 2001/6/12
Y1 - 2001/6/12
N2 - 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.
AB - 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.
KW - Children
KW - Interleukin 2
KW - Neuroblastoma
KW - PBSC
UR - http://www.scopus.com/inward/record.url?scp=0034994174&partnerID=8YFLogxK
U2 - 10.1038/sj.bmt.1702870
DO - 10.1038/sj.bmt.1702870
M3 - Article
C2 - 11477446
AN - SCOPUS:0034994174
SN - 0268-3369
VL - 27
SP - 869
EP - 875
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 8
ER -