On October 2, 2017 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 reported the clinical implementation of the company’s haNK cell therapy program to human clinical trials with the first participants treated in the first-in-human, Phase I haNK cell therapy clinical trial targeting a wide range of cancer types (Press release, NantKwest, OCT 2, 2017, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2303927 [SID1234520745]).

“Only about 10% of individuals are born with a high affinity Natural Killer cell type needed for the maximum killing effect when combined with monoclonal antibodies widely used in clinical practice today such as Trastuzamab, Rituxan and Avulamab. To maximize tumor cell death by this mechanism known as ADCC we have engineered our off the shelf natural killer cell line with a high affinity CD16 receptor. The potential for this haNK cell therapy is to improve patient outcomes for a significant percentage of the other 90% of individuals being treated with antibody therapy in a broad range of tumor types that can now be explored,” said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest.

Dr. Soon-Shiong added, “Our haNK cell therapy program was designed to optimize the unique properties of two immunotherapeutics (a cell based platform with a monoclonal antibody) used as a combination therapy. Multiple published preclinical studies have demonstrated the potential for haNK/antibody combinations to synergistically enhance antibody-dependent cell-mediated cytotoxicity (ADCC) activity, providing a sound scientific rationale for the transition of the haNK program into human clinical trials,” said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest.

haNK Cell Therapy Platform

NantKwest’s haNK cell therapy platform, an allogeneic, off-the-shelf therapy, was developed to optimize the key role of natural killer cells in mediating innate immunity, enhancing adaptive immune responses, and, specifically in the case of haNK, improve anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC is an important part of the human immune system associated with the synergistic interaction of natural killer cells with antibodies to directly kill a target cell that has been identified by an antigen-specific antibody. ADCC represents one of the key mechanisms that antibodies utilize to target and kill cancer cells.

Engineered to express the high-affinity variant of the CD16, high affinity Fc receptor (V158 FcγRIIIa), in multiple published preclinical studies, the combination of haNK cells with a variety of therapeutic antibodies has led to enhanced tumor cell killing when compared to use of the antibody as a single therapeutic agent, providing strong support for this novel combination immunotherapeutic approach.

haNK Phase I Study Background

The primary objective of the Phase I clinical study is to determine the safety of haNK cell therapy administered once per week in up to 16 patients with metastatic or locally advanced solid tumors. Secondary objectives include the determination of objective response rate, progression-free survival, overall survival, and any correlations between tumor molecular profiles (based on genomics, transcriptomics, and quantitative proteomics) and patient outcomes.