Enhanced in vitro and in vivo cytotoxicity of umbilical cord blood cells against human breast cancer following activation with IL-15 and colony stimulating factors

Background: Cord blood mononuclear cells (MNC) are a rich source of precursor cytotoxic effector cells. Earlier we have shown that interleukin-2 (IL-2)-activated MNC from cord blood have significant cytotoxic activity against human leukemia and breast cancer cells in vitro and in vivo, compared to MNC from peripheral blood. Materials and methods: In order to further improve the antitumor cytotoxic ability of cord blood MNC, IL-2 was combined with IL-15 and colony stimulating factors, GMCSF, G-CSF and M-CSF for the activation. The activated cells were examined for their cytotoxic effects in vitro against human breast cancer cell lines MDA-231, MDA453 and SKB43 and in vivo against MDA-231 grown in SCID mice. Phenotypes of these activated cells were determined using flow cytometry. The expression of immune response related genes in activated cells was measured using RT-PCR techniques. Results: There was a significant increase in cytotoxicity of the effector cells activated with IL-2, IL-15 and some colony stimulating factors compared to cells activated with each of these cytokines alone or other combinations. Our results demonstrated the increase in cytotoxicity appears to be due to: 1) increase in CD56-positive cytotoxic cells; 2) cytokine/cytotoxic factors produced by the effector cells, such as Interferon-7 and Perforin; 3) stimulation by accessory cells, such as dendritic cells. In vivo administration of in vitro-activated cord blood cells into SCID mice bearing MDA-231 tumors reduced the number of metastases and increased survival compared to untreated tumor bearing controls. Conclusion: The combination of IL-2 with IL-15 and CSF is better for the activation of cord blood effector cells than to IL-2 alone.