Artiva's platform generates allogeneic natural killer (NK) cells from healthy donor umbilical cord blood (UCB) units selected for key characteristics. Our proprietary, large-scale, campaign-based manufacturing process is capable of producing enough pure and highly active NK cells to treat hundreds to thousands of patients, with the opportunity for repeat dosing, from each UCB. Our NK cells are cryopreserved and ready for off-the-shelf therapeutic use, without the requirement for complex manipulation at the clinical site. We engineer the NK cells to express proprietary chimeric antigen receptors (CARs), optimized for use in NK cells, and/or we combine our NK cells with therapeutic antibodies to further enhance therapeutic activity and specificity for tumor cells. Our ongoing research includes developing novel CAR-NK therapies and optimizing our NK cell products’ activity and persistence through specific gene editing.
Artiva's Advantage: A Platform for the Next Generation of Cell Therapy
Why NK Cell Therapy for Cancer?
Cancer treatment continues to evolve with the use of chemotherapy, molecular therapy, monoclonal antibodies, checkpoint therapy, and antibody drug conjugates and the recent approval of target-specific autologous T-cell therapy (CAR-T). The next generation of cellular immunotherapies includes technologies to adopt and enhance the natural anti-tumor biology of natural killer (NK) cells from the innate immune system.
NK cells are the body’s first line defense against tumor cells, utilizing a complex system of receptors to recognize self from non-self and stress antigens on the surface or tumor cells. On activation, NK cells release perforins and granzymes to kill the target cells and cytokines to recruit and engage other immune cells into anti-tumor activity. NK cells also are the mechanistic mediators of antibody-dependent cellular cytotoxicity, which is guided and activated by tumor-targeting antibody interaction with CD16 on the surface of the NK cells.
Allogeneic NK Cell Therapies Overcome the Challenges of CAR-T
Recent advances in engineered autologous T-cell therapy (CAR-T) have led to demonstrated, transformational anti-tumor activity. However, the complexity, cost, and significant safety challenges of CAR-T therapies could impede their broad adoption. Unlike approved CAR-T therapy, NK cells can be used in an allogeneic, mismatched setting without induction of graft versus host disease (GVHD), potentially enabling the treatment of many patients from the same donor cells. Further, NK cells may have a significantly safer therapeutic profile, compared to the cytokine release syndrome and neurotoxicity seen with CAR-T therapy. However, the NK cell therapy field has been hampered by inadequate manufacturing supply of highly active tumor targeting cells.
Artiva’s proprietary allogeneic NK cell therapy platform utilizes cell expansion and activation technology developed and enhanced for over a decade by our corporate partner GC LabCell. Licensed umbilical cord blood (UCB) units, with prefered characteristics are selected from U.S. cord blood banks. Each UCB is used to derive an NK cell master cell bank followed by a bioreactor-based large-scale NK cell expansion and activation process to produce pure NK cells. The scale of production enables hundreds to thousands of patients to be treated from a single donor UCB and with a cost of production to support wider adoption of a cell therapy product. Optimized cryopreservation of the NK cells in infusion-ready media ensures long term stability, practical logistics, and ease of handling at the clinical site and the opportunity for additional dosing.
The GC family of companies, one of the largest and most successful biopharmaceutical organizations in the Republic of Korea, has invested significantly in state-of-the-art research and GMP manufacturing for the development of cell therapies. GC LabCell is a leader in the field of NK cell biology and has optimized NK cell production and therapeutic application for over a decade. Artiva and GC have established an exclusive partnership to further realize the clinical application of NK cell therapy.
Artiva utilizes a proprietary CAR (chimeric antigen receptor) platform, optimized for use in NK cells, to enhance their therapeutic activity and tumor targeting capability. Multiple costimulatory domains are used in combination with tumor targeting motifs and cytokine co-expression for support of the therapeutic cells. Additionally, all CAR-NK products maintain high expression of CD16, enabling dual targeting therapeutic approaches via monoclonal antibody combinations. We are also evaluating specific gene editing to further enhance the therapeutic activity of NK cells in the tumor microenvironment and methods of potentially enhancing in vivo persistence in the absence of patient lymphodepletion preconditioning regimens.