title: IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer.
abstract: Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production.
  
  
  
  NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells.
  
  
  
  ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor.
  
  
  
  ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer.
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States. Electronic address: mfelices@umn.edu.
authors.forename: M
authors.initials: M
authors.lastname: Felices
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States.
authors.forename: S
authors.initials: S
authors.lastname: Chu
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States.
authors.forename: B
authors.initials: B
authors.lastname: Kodal
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, United States.
authors.forename: L
authors.initials: L
authors.lastname: Bendzick
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, United States.
authors.forename: C
authors.initials: C
authors.lastname: Ryan
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lenvik
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States.
authors.forename: K L M
authors.initials: KLM
authors.lastname: Boylan
authors.affiliation: Altor BioScience Corporation, Miramar, FL, United States.
authors.forename: H C
authors.initials: HC
authors.lastname: Wong
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, United States; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States.
authors.forename: A P N
authors.initials: APN
authors.lastname: Skubitz
authors.affiliation: Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States.
authors.forename: J S
authors.initials: JS
authors.lastname: Miller
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, United States.
authors.forename: M A
authors.initials: MA
authors.lastname: Geller
mesh_terms: D000818:Animals; D001201:Ascites / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000819:agonists*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D011506:Proteins / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins; D023041:Xenograft Model Antitumor Assays
chemical_list: C582303:ALT-803; D019409:Interleukin-15; D011506:Proteins; D011993:Recombinant Fusion Proteins
keywords: IL-15 super-agonist; Immunotherapy; Natural killer cells; Ovarian cancer