N-803 Boosts CD34+ Progenitor-Derived NK Cell Expansion and Functionality
Adding N-803 to NK Cell Therapy has Potential to Improve Cancer Immunotherapy
CULVER CITY Calif., November 23, 2020 — ImmunityBio, a privately-held immunotherapy company, today announced the publication in Cancer Immunology, Immunotherapy of preclinical data demonstrating that ImmunityBio’s AnktivaÔ (IL-15 superagonist also known as N-803) improves interferon-gamma (IFN-g) production and killing of tumor of cells in vitro and in vivo by CD34+ progenitor-derived natural killer (NK) cells. Anktiva is currently being evaluated in late-stage clinical trials in combination with NantKwest’s (NASDAQ: NK) NK cell therapies for multiple indications including metastatic pancreatic cancer, triple negative breast cancer (TNBC), bladder cancer and lung cancer.
“While allogeneic NK cell therapy is a promising and potentially paradigm-shifting approach for cancer immunotherapy, there are still considerable challenges remaining in the field,” said Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio. “One way to boost NK cell function is through the use of IL-15, however, its short in vivo half-life limits its utility in the clinic. Anktiva was developed to overcome the limitations of IL-15 to fully unleash the potential of NK cell immunotherapy. These preclinical data are an important step forward in demonstrating the potential of Anktiva to boost NK cell functionality by increasing the production of key cytokines and improving killing properties across diverse in vitro and in vivo cancer models. Importantly, these data provide validating proof-of-mechanism that support the encouraging clinical data observed to date when combining Anktiva with NantKwest’s NK cell therapies across a range of challenging solid tumors with poor prognoses. We look forward to the continued evaluation of Anktiva as a promising IL-15 superagonist, which may be broadly applied to improve NK cell-based immunotherapies.”
Key findings from the study performed under the guidance of Prof. Harry Dolstra at the Radboud Institute for Molecular Life Sciences in The Netherlands, reported in the publication titled, “IL‐15 superagonist N‐803 improves IFN-g production and killing of leukemia and ovarian cancer cells by CD34+ progenitor‐derived NK cells” include:
- Anktiva induces HPC-NK cell proliferation in a dose-dependent manner;
- Treatment with Anktiva increases IFN-g production in CD34+ hematopoietic progenitor-derived NK cells (HPC-NK) stimulated with leukemia cells lines and improves killing of primary AML samples from patients;
- Anktiva improves serial killing properties of HPC-NK cells against leukemia as measured by live cell imaging with single cell resolution;
- Anktiva increases CXCL10 production and improves long-term HPC-NK cell-mediated killing in ovarian cancer spheroids, an ovarian cancer model which mimics three-dimensional growth of ovarian cancer in vivo;
- HPC-NK cells combined with Anktiva and nanogam (human immunoglobulins) show anti-tumor effects in a human ovarian cancer mouse model;
Together, these data point to the clear potential of AnktivaÔ to improve efficacy of NK cell-based immunotherapies by promoting HPC-NK cell expansion and functionality.
ImmunityBio, Inc. is a late-stage immunotherapy company developing next-generation therapies that drive immunogenic mechanisms for defeating cancers and infectious disease. The company’s immunotherapy platform activates both the innate (natural killer cell and macrophage) and adaptive (T cell) immune systems to create long-term “immunological memory.” This novel approach is designed to eliminate the need for high-dose chemotherapy, improve upon the outcomes of current CAR T-cell therapies, and extend beyond checkpoint inhibitors.
ImmunityBio has established three fundamental platforms to drive long term immunological memory. These include first-in-class antibody cytokine fusion proteins, synthetic immune modulators, and second-generation vaccine vector platforms.
ImmunityBio’s lead cytokine infusion protein, a novel interleukin-15 (IL-15) superagonist complex (AnktivaÔ), has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for BCG-unresponsive CIS non-muscle invasive bladder cancer (NMIBC). Other indications currently at registration-stage trials include BCG-unresponsive papillary bladder cancer, first- and second-line lung cancer, triple-negative breast cancer, metastatic pancreatic cancer, recurrent glioblastoma, and soft tissue sarcoma in combination with the company’s synthetic immune modulator (Aldoxorubicin).
ImmunityBio is also developing therapies, including vaccines, for the prevention and treatment of HIV, influenza, and the coronavirus SARS-CoV-2 with its second-generation human adenovirus (hAd5) vaccine platform.
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