Natural killer cell therapy and aerosol interleukin‐2 for the treatment of osteosarcoma lung metastasis. Issue 4 (18th October 2013)

• Record Type: Journal Article
• Authors: Guma, Sergei R.; Lee, Dean A.; Yu, Ling; Gordon, Nancy; Hughes, Dennis; Stewart, John; Wang, Wei Lien; Kleinerman, Eugenie S.
• Is Part Of: Pediatric blood & cancer. Volume 61:Issue 4(2014:Apr.)
• Page Start: 618
• Page End: 626
• Publication Date: 2013-10-18
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.24801
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="pbc24801-sec-0001" sec-type="section"> <title>Background</title> <p>Survival of patients with osteosarcoma lung metastases has not improved in 20 years. We evaluated the efficacy of combining natural killer (NK) cells with aerosol interleukin‐2 (IL‐2) to achieve organ‐specific NK cell migration and expansion in the metastatic organ, and to decrease toxicity associated with systemic IL‐2.</p> </sec> <sec id="pbc24801-sec-0002" sec-type="section"> <title>Procedure</title> <p>Five human osteosarcoma cell lines and 103 patient samples (47 primary and 56 metastatic) were analyzed for NKG2D ligand (NKG2DL) expression. Therapeutic efficacy of aerosol IL‐2 + NK cells was evaluated <italic>in vivo</italic> compared with aerosol IL‐2 alone and NK cells without aerosol IL‐2.</p> </sec> <sec id="pbc24801-sec-0003" sec-type="section"> <title>Results</title> <p>Osteosarcoma cell lines and patient samples expressed various levels of NKG2DL. NK‐mediated killing was NKG2DL‐dependent and correlated with expression levels. Aerosol IL‐2 increased NK cell numbers in the lung and within metastatic nodules but not in other organs. Therapeutic efficacy, as judged by tumor number, size, and quantification of apoptosis, was also increased compared with NK cells or aerosol IL‐2 alone. There were no IL‐2‐associated systemic toxicities.</p> </sec> <sec id="pbc24801-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Aerosol IL‐2 augmented the efficacy of NK cell therapy against osteosarcoma lung metastasis, without inducing systemic toxicity. Our data suggest that lung‐targeted IL‐2 delivery circumvents toxicities induced by systemic administration. Combining aerosol IL‐2 with NK cell infusions, may be a potential new therapeutic approach for patients with osteosarcoma lung metastasis. Pediatr Blood Cancer 2014;61:618–626. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>