IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer

M. Felices, S. Chu, B. Kodal, L. Bendzick, C. Ryan, A. J. Lenvik, K. L M Boylan, H. C. Wong, A. P N Skubitz, J. S. Miller, M. A. Geller

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objective 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)453-461
Number of pages9
JournalGynecologic Oncology
Volume145
Issue number3
DOIs
StatePublished - Jun 1 2017

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Interleukin-15
Natural Killer Cells
Ovarian Neoplasms
Ascites
ALT-803
Cell Line
Chromium
Blood Cells
Neoplasms
Flow Cytometry
Tissue Donors
Cytokines

Keywords

  • IL-15 super-agonist
  • Immunotherapy
  • Natural killer cells
  • Ovarian cancer

Cite this

IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. / Felices, M.; Chu, S.; Kodal, B.; Bendzick, L.; Ryan, C.; Lenvik, A. J.; Boylan, K. L M; Wong, H. C.; Skubitz, A. P N; Miller, J. S.; Geller, M. A.

In: Gynecologic Oncology, Vol. 145, No. 3, 01.06.2017, p. 453-461.

Research output: Contribution to journalArticle

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abstract = "Objective 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. Methods 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. Results 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. Conclusions 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.",
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AU - Ryan, C.

AU - Lenvik, A. J.

AU - Boylan, K. L M

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