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.
Discussion: 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.