Next Generation NK Cell Therapy Poised to Transition into Human Clinical Trials
The study’s results highlight the key role natural killer (NK) cells play in mediating innate immunity and enhancing adaptive immune responses, as well as anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) by activation of the CD16 high affinity receptor with the Fc region of human IgG1 antibodies.
In this research study, aNK (NK-92) cells, lacking CD16, were engineered to express the high affinity CD16 receptor (V158 FcγRIIIa) and further engineered to express IL-2. These high affinity NK (haNK) cells, have been shown in previous studies to enhanced perforin and granzyme-mediated killing of tumor cells, as well as support the expansion of NK cell populations.
Study results showed high levels of granzyme activity in haNK cells and demonstrated the effects of irradiation on haNK cell in multiple phenotypic markers, viability, IL-2 production, and cell killing in a wide range of human tumor cells. The study also compared endogenous irradiated haNK cell killing of tumor cells with that of irradiated haNK-mediated ADCC using cetuximab, trastuzumab and pertuzumab monoclonal antibodies.
The senior author of the study,
Echoing Dr. Schlom’s conclusion,
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
Jen Hodson, 562-397-3639