• NantKwest’s antibody-targeted NK cell line, haNK, which is engineered for increased antibody-dependent cell-mediated cytotoxicity and activation, showed increased resistance to hypoxic conditions as seen in suppressive tumor microenvironments
  • NantKwest’s PD-L1 t-haNK cells, haNK cells engineered to express PD-L1 checkpoint-directed chimeric antigen receptors, demonstrated in-vivo tumor trafficking, significant elimination of both monocytic and granulocytic MDSCs and demonstrated robust anti-tumor activity in cancer cell lines and in mouse models
  • Studies demonstrated the ability of PD-L1 t-haNK to kill 20 out of 20 human cancer cell lines tested, including triple negative breast cancer (TNBC) and lung, urogenital, and gastric cancer cells

EL SEGUNDO, CA, USA I June 10, 2020 I NantKwest, Inc. (Nasdaq: NK), a clinical-stage, natural killer cell-based therapeutics company, today announced the publication of two peer-reviewed manuscripts in the Journal of Immunotherapy of Cancer. These invitro and in-vivo studies, conducted in collaboration with the National Cancer Institute pursuant to a Cooperative Research and Development Agreement, support the mechanism and functionality of NantKwest’s clinical-stage engineered natural killer (NK) cell lines, haNK® and first-in-class PD-L1 t-haNKTM, as effecting anti-tumor activity in treatment-refractory cancer types even in the hypoxemic setting of the solid tumor microenvironment.

“These published studies provide important insight and validation for the mechanism and activity of our novel first-in-class engineered NK cells for use in notoriously difficult solid tumor types,” said Patrick Soon-Shiong, M.D., Chairman and Chief Executive Officer of NantKwest. “NK cells have the potential to kill tumor cells; however, the hypoxic nature of the suppressive tumor environment has been shown to curb primary NK cell function. These published data indicate that our engineered haNK cells remain active in hypoxic conditions, which may be an important new mechanism of its anti-tumor activity. In addition, our NK cells appear to be resistant even to acute hypoxia and are capable of maintaining tumor killing activity in conditions comparable to a suppressive tumor microenvironment.”

Dr. Soon-Shiong continued, “In addition, we are encouraged to observe anti-tumor activity in every cancer cell line tested by the investigators at NCI. The positive data in the in-vivo models of solid tumors with PD-L1 t-haNK, our engineered haNK cell line that also expresses a PD-L1 CAR, provides a novel approach to target tumors expressing PD-L1. This highly targeted NK cell therapy has the potential to address the evolution of tumors as they become resistant to chemotherapy, antibody therapy and, ultimately, checkpoint immunotherapy. We have hypothesized that cancer undergoes a quantum change and adapts to the therapy administered, resulting in the selection of resistant, cancer stem-like cells. It is at this stage of evolution where intractable tumors such as in patients with metastatic pancreatic cancer and triple negative breast cancer, are deemed incurable. It is our belief that these cancer “stem” cells, which do not divide and hence are untouchable by chemotherapy, become resistant and render checkpoint therapy futile by not expressing t-cell receptor ligands. In the face of this immunosuppressive milieu, our PD-L1 t-haNK cells can act to kill these otherwise highly resistant cancer cells, as demonstrated by these two important reports by our colleagues at the NCI. Our clinical results in the first patient with advanced metastatic pancreatic cancer to have received PD-L1 t-haNK demonstrated a durable complete response.”

Study highlights from the publication titled “Overcoming hypoxia-induced functional suppression of NK cells” include:

  • NantKwest haNK cells engineered to express a high-affinity CD16 receptor as well as internal interleukin (IL)-2 for increased antibody-dependent cellular cytotoxicity (ADCC) and activation maintained killing activity under hypoxic conditions comparable to those of the suppressive tumor microenvironment, while healthy donor NK cell activity was significantly impaired
  • NK killing, serial killing and ADCC were maintained under hypoxia in haNK cells
  • haNK cells’ IL-2 is likely a driver of maintained killing capacity under hypoxic conditions

Study highlights from the article titled “PD-L1-targeting high-affinity NK cells (PD-L1 t-haNK) induce direct antitumor effects and target suppressive MDSC populations” include:

  • PD-L1.t-haNK cells engineered to express a high-affinity CD16 receptor, an internal interleukin (IL)-2 and PD-L1-specific chimeric antigen receptor (CAR) broke down all 15 human tumor cell lines tested, including those modelling historically treatment-refractory cancers (triple negative breast cancer, lung, and urogenital cancer)
  • In vitro, the cytotoxicity of PD-L1 t-haNK cells was correlated to the PD-L1 expression of the tumor targets
  • In mouse models of solid tumors, PD-L1 t-haNK inhibited the growth of engrafted TNBC, lung and bladder tumors in mice without toxicity

The articles may be found on the Publications section of the NantKwest corporate website here: https://nantkwest.com/peer-reviewed-publications/

About NantKwest
NantKwest (NASDAQ: NK) is an innovative, clinical-stage immunotherapy company focused on harnessing the power of the innate immune system to treat cancer and virally-induced infectious diseases. NantKwest is the leading producer of clinical dose forms of off-the-shelf natural killer (NK) cell therapies. The activated NK cell platform is designed to destroy cancer and virally-infected cells. The safety of these optimized activated NK cells—as well as their activity against a broad range of cancers—has been tested in Phase I clinical trials in Canada and Europe, as well as in multiple Phase I and II clinical trials in the United States. By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs, NantKwest’s goal is to transform medicine by delivering off-the-shelf, novel NK cell-based therapies to routine clinical care. NantKwest is a member of the NantWorks ecosystem of companies. For more information, please visit www.nantkwest.com.

SOURCE: Nantkwest