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

M Felices1, S Chu1, B Kodal1

  • 1Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States.

Gynecologic Oncology
|February 26, 2017
PubMed
Abstract

Insights

The IL-15 super-agonist ALT-803 enhances natural killer (NK) cell activity against ovarian cancer. This immunotherapy approach boosts NK cell cytotoxicity and cytokine production, showing potential for ovarian cancer treatment.

Area of Science:

  • Immunology
  • Cancer Biology
  • Pharmacology

Background:

  • Natural killer (NK) cells are crucial for direct tumor lysis and immune responses, making them a promising immunotherapeutic target.
  • Ovarian cancer presents challenges for effective immunotherapy due to potential NK cell dysfunction in patients.

Purpose of the Study:

  • To investigate the efficacy of ALT-803, an IL-15 super-agonist complex, in enhancing the function of normal and ovarian cancer patient-derived NK cells.
  • To assess ALT-803's ability to increase NK cell cytotoxicity and cytokine production against ovarian cancer cells.

Main Methods:

  • NK cell function was evaluated using flow cytometry and chromium release assays with peripheral blood mononuclear cells and ascites-derived NK cells from ovarian cancer patients, with and without ALT-803 stimulation.
  • A xenogeneic mouse model (MA148-luc ovarian cancer in NSG mice) with transferred human NK cells was used to assess ALT-803's in vivo efficacy.

Main Results:

  • ALT-803 significantly enhanced NK cell functionality, increasing cytotoxicity and expression of CD107a, IFNγ, and TNFα against ovarian cancer cell lines.
  • NK cell function was restored in cells derived from ovarian cancer patient ascites.
  • Intraperitoneal administration of ALT-803 led to a significant, NK cell-dependent reduction in tumor growth in the mouse model.

Conclusions:

  • ALT-803 effectively enhances NK cell-mediated cytotoxicity against ovarian cancer both in vitro and in vivo.
  • The compound demonstrates the ability to rescue the function of NK cells from the ascites of ovarian cancer patients.
  • ALT-803 shows significant potential as an adjunct therapy to augment NK cell-based immunotherapeutic strategies for ovarian cancer.
Keywords:
IL-15 super-agonistImmunotherapyNatural killer cellsOvarian cancer

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