Description:
Abstract Despite the efficacy of hematopoietic stem cell transplantation (HSCT) as a cancer therapy, cancer relapse remains a significant complication. Natural killer (NK) cells are the first lymphoid population to recover after HSCT and can kill transformed or virally-infected cells without prior sensitization. Therefore, accelerating NK cell reconstitution may improve HSCT therapy. We utilized the combination of administering the stimulatory cytokine, IL-2 concurrently with the blockade of the immunosuppressive cytokine, transforming growth factor-beta (TGF-β) as a possible therapy to accelerate NK cell reconstitution after syngeneic HSCT. Resting C57BL/6 mice were treated with daily doses of IL-2 (2x105 IU) and anti-TGF-β (120ug, clone 1D11) every other day for one week. Although combinatorial therapy did not significantly expand NK cell numbers in comparison with IL-2 monotherapy, NK cytotoxicity, as measured by the ability to lyse Yac-1 tumor cells, was significantly greater. However in a HSCT model, combinatorial therapy administered in C57BL/6 mice starting at day 11 post-HSCT did significantly increase both the percentage of activated NK cells and NK tumor lytic ability compared with IL-2 alone. Additionally, mice showed no outward evidence of toxicity during administration of therapy. Together, these results suggest that this combination regimen improves reconstitution of NK cells after HSCT which may lead to better anti-viral and anti-tumor responses.