Interview: Harnessing the Power of the Innate Immune System Using NK Cells

Dr. Klingemann is currently VP of research and development at NantKwest (Nasdaq: NK), the company he founded in 2002 as Zellerx based on the core technology of NK-92. He is the former director of the bone marrow and stem cell transplant program at boston’s tufts medical center and the cancer center’s hematological malignancies program

NantKwest is a clinical-stage immunotherapy company focused on harnessing the power of the innate immune system with a focus on using NK Cells.The company presented data on the first generation of GMP-grade NK Cell Line for combination immunotherapy at a recent AACR meeting. Why is this such an exciting avenue for R&D focus in the immuno-oncology field?

Nantkwest is currently in a phase II trial with the parental, non-engineered aNK cells in patients with advanced Merkel Cell Cancer. The aNK cells don't express the high-affinity FcR receptor. We now have developed a next-generation NK cell therapy that we call haNK cell therapy which includes the high-affinity Fc-receptor which upon binding to monoclonal antibodies further enhances their activity and functionality. This is particularly relevant for the 90% of the patients who do not express the high-affinity FcR on their own NK cells. Studies have shown that the high-affinity FcR expressed on NK cells improves outcome with combination therapy with antibody therapy such as Rituxan, Herceptin and other antibodies


We are now reaching the stage where researchers are saying they have had some great results in advanced NSCLC & Melanoma with immunotherapies; how are we going to extend these benefits to other disease states? For a company as innovative and thought-leading as NantKwest, what do you believe are the next steps?

The checkpoint inhibitors and the CAR-T cell therapies have clearly brought benefits to patients with certain diseases, but we have also seen at times significant side effects. To us, it is rewarding to see responses to NantKwest's aNK cell infusions in patients who had failed checkpoint inhibitors and other therapies. Clearly, the future in combination treatment is to provide synergistic and non-crossreactive immunotherapies similar to what we seek to accomplish with combinations of single-agent chemotherapy.


With the focus on combination therapies now in immuno-oncology, what are the major challenges for researchers to make these partnerships work?

There are a number of challenges such as providing patients access to drugs from multiple companies, developing clinical protocols that optimise therapeutic effects from each drug, simplifying the institutional IRB process and ultimately gaining FDA approval for these unique drug combinations that will demonstrate improved patient outcomes without increasing the risk to the patient.


Do you see more numerous and greater collaboration between diagnostic companies and biotech as this oncology area moves forward?

This is an absolute necessity, both internally and externally. At NantKwest, we benefit from internal collaborations with NantHealth, which is providing information technology and decision support tools, and Nantomics, which is providing multi-omics, genomic sequencing and proteomics molecular diagnostics that enhance our ability to optimize therapeutic interventions. Externally, through the Cancer MoonShot 2020 program, we continue to seek to build a greater network of collaborations that will allow us to bring novel and more effective NK cell-based therapeutics to patients.

Dr Hans Klingemann, VP R&D, NantKwest
Dr Hans Klingemann, VP R&D, NantKwest