IL-2-activated cord blood mononuclear cells.
BACKGROUND
[corrected] Recent findings in cord blood (CB) research indicate the potential clinical usefulness of IL-2-activated CB in eradication of minimal malignant residual disease after hematopoietic stem cell transplantation. This feasible approach to immunotherapy merits further pre-clinical investigations using human tumor models of hematologic malignancy.


METHODS
The aim of our study was to compare the anti-tumor potential of CB mononuclear cells (MNC), matured in the presence of IL-2, to BM, and to determine phenotype and cytokine secretion in IL-2 CB MNC culture during the peak of their anti-leukemia cytotoxic activity. Phenotype change was analysed with flow cytometry, cytokine secretion with ELISA tests and cytotoxic activity with cytotoxicity assays.


RESULTS
Following IL-2 maturation, the phenotype of CB MNC was remarkably changed. Lengthening IL-2 culture to 8 days significantly increased CD8+, CD16+ CD56+, CD56+ and CD56+ CD8+ populations. Interestingly, FACS analyzes revealed the occurrence of CD8+ CD56+ cells that were not present in non-stimulated CB. Cultures progressively produced higher levels of INF-gamma, TNF-alpha and GM-SCF. The IL-2-activated cells manifested potent lytic capabilities against both NK- and LAK-sensitive tumor cell targets.


CONCLUSIONS
At the peak of cytotoxic activity during 8-day IL-2 CB MNC culture, we found increased numbers of various cytotoxic cells and increased secretion of cytokines that may contribute further to their potential therapeutic effect. The duration of CB IL-2 cultures may be crucial for successful application of CB in transplant situations to boost the CB GvL.
Derzic
S
S
Children's Hospital of Orange County Research Institute, Orange, California 91006, USA.
Slone
V
V
Sender
L
L
D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor