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|NantKwest Announces Successful First in Human Administration of CD16 High Affinity Natural Killer (haNK) Cells|
Successful Administration Of Off The Shelf Hank Cells In Patients With Solid Tumors Paves The Way To Nation's First Combination Innate And Adaptive NANT Cancer Vaccine Trials In Multiple Tumor Types
"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
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
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.
For additional information, including exclusion and inclusion criteria, contact information and other details, please visit www.clinicaltrials.gov, QUILT trial #3.028.
NantKwest’s unique NK cell-based platform, with the capacity to grow active killer cells as a biological cancer therapy, has been designed to induce cell death against cancer or infected cells by three different modes of action: (1) Direct killing using activated NK cells (aNK) that release toxic granules directly into the cell through cell to cell contact, (2) Antibody-mediated killing using haNKs, which are NK cells engineered to incorporate a high affinity receptor that binds to an administered antibody, enhancing the cancer cell killing effect of that antibody, and (3) Targeted activated killing using taNKs, which are NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells.
Our aNK, haNK and taNK platform addresses certain limitations of T cell
therapies including the reduction of risk of serious "cytokine storms"
reported after T cell therapy. As an “off-the-shelf” therapy,
By leveraging an integrated and extensive genomics and transcriptomics
discovery and development engine, together with a pipeline of multiple,
clinical-stage, immuno-oncology programs that include a Phase 2 trial
for a rare form of melanoma and the planned initiation of a clinical
trial of NK cells targeted to breast cancer, we believe