NantKwest is an innovative clinical-stage immunotherapy company focused on harnessing the power of the innate immune system by using the natural killer cell to treat cancer, infectious diseases and inflammatory diseases.
NantKwest is uniquely positioned to implement precision cancer medicine, with the potential to change the current paradigm of cancer care. Natural Killer cells are ancient cells in the human body designed to recognize and detect cells under stress or infected. Our "off-the-shelf" activated Natural Killer (NK) platform have the capacity to destroy cancer and virally infected cells from the body. The safety of our NK cells as well as their activity against a broad range of cancers have been tested in multiple phase 1 clinical trials in the United States, Canaa and Europe. In addition to our NK cells capability to be administered in the outpatient setting as an “off-the-shelf” living drug, it serves as a universal cell-based therapy without need for individualized patient matching. Moreover, our NK cell based platform has been bioengineered to incorporate chimeric antigen receptors (CARs) and antibody receptors to further optimize targeting and potency in the therapeutic disease.
A Next Generation Immuno Therapy Platform:
A Living Drug - Delivered in a Blood Bag with Multiple Modes of Killing
Overview: The Natural Killer Cell
The immune system is a tapestry of diverse families of immune cells each with its own distinct role in protecting from infections and diseases. Among these immune cells are the natural killer, or NK, cells as the body’s first line of defense. NK cells have the innate ability to rapidly seek and destroy abnormal cells, such as cancer or virally-infected cells, without prior exposure or activation by other support molecules. In contrast to adaptive immune cells such as T cells, NK cells are uniquely powerful in that they are always activated to attack diseased cells, without a delay in killing. Our proprietary activated Natural Killer (aNK) platform is based upon highly potent Natural Killer cells from a unique cell line, harnessing the power of the innate immune system.
Activated Natural Killer "Off-The-Shelf" Cell: The aNK Cell
Our unique NK cell platform has been produced and utilized as a cell-based “off-the-shelf” treatment in phase 1 clinical trials, and has demonstrated tumor killing abilities for cancer. Unlike normal NK cells, our unique NK cells do not express Killer Inhibitory Receptors (KIR), which diseased cells often exploit to evade the killing function of NK cells. We have optimized this unique activated NK, or aNK, cell which lack these inhibitory receptors while retaining the broad array of activating receptors which enable the selective targeting and killing of diseased cells. aNK cells also carry a larger pay load of granzyme and perforin containing granules, thereby enabling them to deliver a far greater payload of lethal enzymes to multiple targets.
Natural Killer (NK) Cell: Mechanism of Action and Innate Killing
We are developing means by which our aNK cells can be grown at commercial scale as on-demand, ‘Living Drug in a Bag’, using our proprietary manufacturing and distribution processes.
Delivering Living Drugs in a Bag
Safety studies of aNK cells in dozens of patients treated in Phase I clinical trials have been conducted in a variety of advanced hematological malignancies and solid tumors. Encouraging evidence of safety, activity and prolonged survival have been demonstrated. Based on these clinical trials, we plan to develop the therapeutic applications of our aNK platform through genetic engineering of our aNK cells designed to leverage the multiple modes of killing available to aNKs, including high affinity antibody targeting, our haNK platform, and tumor antigen targeting, our taNK platform.
Antibody Mediated Cell Killing by high-affinity Natural Killer cells: haNK
Blockbuster monoclonal antibody therapies such as Herceptin® (trastuzumab) or Rituxan® (Rituximab)[1] specifically target cancer cells, thus avoiding adverse events that are common with chemotherapy. However, much of the cancer cell killing relies upon ADCC (antibody dependent cell-mediated cytotoxicity) whereupon effector immune cells attach to antibodies, which are in turn bound to the target cancer cell, thereby facilitating killing of the cancer by the effector cell. NK cells are the key effector cell in the body for ADCC and utilize a specialized receptor (CD16) to bind antibodies.
Studies have shown that perhaps only 20% of the human population uniformly expresses the “high-affinity” variant of CD16, which is strongly correlated with more favorable therapeutic outcomes compared to patients with the “low-affinity” CD16. Additionally, many cancer patients have severely weakened immune systems due to chemotherapy, the disease itself or other factors.
We have modified haNK cells to express high-affinity CD16. As such, haNK cells may potentiate the therapeutic efficacy of a broad spectrum of antibodies directed against cancer cells. We are actively advancing haNK with plans to initiate our first clinical trial in 2016.
[1] Herceptin and Rituxan are registered trademarks of Genentech.
Target-Activated Natural Killer Cell: taNK
Chimeric antigen receptor (CAR) technology is among the most novel cancer therapy approaches currently in development. CARs are proteins that allow immune effector cells to target cancer cells displaying specific surface antigens.
taNK (target-activated Natural Killer) is a platform in which our aNK cells are engineered with one or more CARs to target proteins found on cancers and is then integrated with a wide spectrum of CARs. This strategy has multiple advantages over other CAR approaches using patient or donor sourced effector cells such as autologous T-cells, especially in terms of scalability, quality control and consistency.
Our most advanced taNK cell line expresses a CAR for ErbB2 (also known as Her2), a protein commonly found on breast, ovary, gastric, bladder and medulloblastoma (brain) cancers. Other taNK programs are in various stages of development.
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