In this study, haNK cells, which are NantKwest’s proprietary NK cells, engineered to express the IL-2 cytokine and the high affinity CD16 allele, have been combined with avelumab, a human IgG1 anti-PD-L1 antibody.
Consistent with previous studies, results demonstrate the enhanced cancer cell killing abilities of haNK cells in combination with avelumab in a range of cancer cell types via the antibody dependent cell-mediated cytotoxicity (ADCC) mechanism.
ADCC is part of the human cell-mediated immune defense system associated with the interaction of natural killer cells with antibodies to directly kill a target cell that has been identified by an antigen-specific antibody. It is one of the key mechanisms that antibodies utilize to target and kill cancer cells.
In addition, engineering haNK cells to express IL-2 enables a “serial killer like” capacity, killing greater levels of target cells by increasing the exposure to target cells and increasing activity while also replenishing the granular stock of NK cells, enhancing the granzyme-mediated lysis of NK cells which exhibit an exhausted phenotype.
Of note, consistent with previous studies with haNK cells, this study demonstrated that activity, cytotoxicity and immune signaling capabilities of haNK cells remained intact post-irradiation.
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, improving anti-tumor responses via antibody-dependent cell-mediated cytotoxicity.
To achieve this objective, haNK cells have been engineered to express the IL-2 cytokine and the high-affinity variant of the CD16 receptor (V158 FcγRIIIa). In preclinical studies, the addition of haNK to a variety of therapeutic antibodies has led to increased tumor cell killing when compared to the antibody alone. Human clinical studies are designed to provide the necessary safety data to rapidly transition the haNK Phase I safety study to haNK-antibody combination trials as quickly as possible.
haNK Phase I Study Background
The primary objective of the Phase I study is to determine the safety of haNK cell monotherapy administered intravenously 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.
A second haNK clinical trial, QUILT trial #3.046, NANT Melanoma Vaccine: Combination Immunotherapy in Subjects with Melanoma Who Have Progressed On or After Chemotherapy and PD-1/PD-L1 Therapy, was also recently been posted on clinicaltrials.gov and will be open for participant recruitment in the next few months.
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