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Nguyen, Rosa; Moustaki, Ardiana; Norrie, Jacqueline L; Brown, Shantel; Akers, Walter J; Shirinifard, Abbas; Dyer, Michael A
Clinical cancer research, 12/2019, Letnik: 25, Številka: 24Journal Article
Immunotherapy with IL2, GM-CSF, and an anti-disialoganglioside (GD2) antibody significantly increases event-free survival in children with high-risk neuroblastoma. However, therapy failure in one third of these patients and IL2-related toxicities pose a major challenge. We compared the immunoadjuvant effects of IL15 with those of IL2 for enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) in neuroblastoma. We tested ADCC against neuroblastoma patient-derived xenografts (PDX) and and examined the functional and migratory properties of NK cells activated with IL2 and IL15. In cell culture, IL15-activated NK cells induced higher ADCC against two GD neuroblastoma PDXs than did IL2-activated NK cells ( < 0.001). This effect was dose-dependent ( < 0.001) and was maintained across several effector-to-tumor ratios. As compared with IL2, IL15 also improved chemotaxis of NK cells, leading to higher numbers of tumorsphere-infiltrating NK cells ( = 0.002). In an orthotopic PDX model, animals receiving chemoimmunotherapy with an anti-GD2 antibody, GM-CSF, and a soluble IL15/IL15Rα complex had greater tumor regression than did those receiving chemotherapy alone ( = 0.012) or combined with anti-GD2 antibody and GM-CSF with ( = 0.016) or without IL2 ( = 0.035). This was most likely due to lower numbers of immature tumor-infiltrating NK cells (DX5 CD27 ) after IL15/IL15Rα administration ( = 0.029) and transcriptional upregulation of . The substitution of IL15 for IL2 leads to significant tumor regression and and supports clinical testing of IL15 for immunotherapy in pediatric neuroblastoma.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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