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Biol Blood Marrow Transplant. 2008 Oct;14(10):1088-1099. doi: 10.1016/j.bbmt.2008.08.001.

Combination therapy using IL-2 and anti-CD25 results in augmented natural killer cell-mediated antitumor responses.

Author information

1
Department of Microbiology and Immunology, University of Nevada School of Medicine, University of Nevada Reno, Reno, Nevada.
2
University of Minnesota Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis, Minnesota.
3
Department of Microbiology and Immunology, University of Nevada School of Medicine, University of Nevada Reno, Reno, Nevada. Electronic address: wmurphy@medicine.nevada.edu.

Abstract

Interleukin (IL)-2 has been extensively examined to promote clinical T and natural killer (NK) cell responses. Regulatory T cells (Tregs) have been shown to regulate many aspects of the immune system, including NK cell-mediated responses. We have demonstrated that in vivo administration of IL-2 led to activation and expansion of both NK cells and immunosuppressive Tregs. Therefore, we attempted to augment NK cell antitumor effects by concurrently depleting Tregs using anti-CD25. Increased NK cell activation by IL-2 was found to be correlated with an increase in classical, short-term NK cell in vitro killing assays regardless of the depletion of Tregs. But when splenocytes of the treated mice were used in long-term tumor outgrowth experiments, we observed that prior depletion of Tregs from IL-2 administration led to improved antitumor effects compared with either treatment alone. Importantly, these in vitro data are correlated with subsequent in vivo survival of leukemia-bearing mice, in which co-treatment of IL-2 with anti-CD25 led to significantly improved survival compared with mice treated with either IL-2 alone or with Treg depletion. Prior depletion of NK1.1(+) cells, but not of CD8(+) cells, completely abrogated all antitumor effects mediated by IL-2 and anti-CD25 combination therapy. These findings demonstrate that superior NK cell-mediated antileukemic effects can be achieved with IL-2 administration and concurrent depletion of CD25(+) cells.

PMID:
18804038
PMCID:
PMC2735407
DOI:
10.1016/j.bbmt.2008.08.001
[Indexed for MEDLINE]
Free PMC Article

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