In vitro generation of cytotoxic effectors activated by interleukin 2 (IL-2): comparison of autologous peripheral blood stem cells (PBSC) from adults and children.
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.
Valteau-Couanet
D
D
Pediatrics Department, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
Angevin
E
E
Leboulaire
C
C
Beaussier
P S
PS
Bayle
C
C
Hartmann
O
O
Beaujean
F
F
D000328:Adult; D000367:Age Factors; D001772:Blood Cell Count; D001773:Blood Cells / Q000166:cytology / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods; D002648:Child; D003601:Cytotoxicity Tests, Immunologic; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007376:Interleukin-2; D018664:Interleukin-12