On November 22, 2016 NantKwest Inc. (Nasdaq:NK), a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of the immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases, reported in a paper published today in the journal Oncotarget results of a research study conducted at the National Cancer Institute (NCI) in collaboration with scientists at NantKwest and NantCell (Press release, NantKwest, NOV 22, 2016, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2225326 [SID1234516766]). The title of the paper is: An NK cell line (haNK) expressing high levels of granzyme and engineered to express the high affinity CD16 allele.
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The study’s results highlight the key role natural killer (NK) cells play in mediating innate immunity and enhancing adaptive immune responses, as well as anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) by activation of the CD16 high affinity receptor with the Fc region of human IgG1 antibodies.
In this research study, aNK (NK-92) cells, lacking CD16, were engineered to express the high affinity CD16 receptor (V158 FcγRIIIa) and further engineered to express IL-2. These high affinity NK (haNK) cells, have been shown in previous studies to enhanced perforin and granzyme-mediated killing of tumor cells, as well as support the expansion of NK cell populations.
Study results showed high levels of granzyme activity in haNK cells and demonstrated the effects of irradiation on haNK cell in multiple phenotypic markers, viability, IL-2 production, and cell killing in a wide range of human tumor cells. The study also compared endogenous irradiated haNK cell killing of tumor cells with that of irradiated haNK-mediated ADCC using cetuximab, trastuzumab and pertuzumab monoclonal antibodies.
The senior author of the study, Jeffrey Schlom, PhD, Chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute, commenting on the results, said the following: "We believe these studies provide a strong rationale for the potential use of haNK cells in NK cell-based therapy for a wide range of human tumor types. In addition, since only about 10% of humans are homozygous for the high affinity V CD16 allele, this study also establishes a strong rationale for the use of haNK cells in combination with IgG1 based monoclonal antibodies."
Echoing Dr. Schlom’s conclusion, Patrick Soon-Shiong, MD, PhD, Chairman and CEO of NantKwest and a co-senior author on the paper said the following: "Ongoing preclinical studies using haNK cell therapy in combination with antibody therapy offer the promising potential to enhance the clinical efficacy of either agent alone and become a part of the standard-of-care for cancer patients. With this foundational data in place, we on now focused on rapidly transitioning our haNK program into human clinical trials over the next few months."