Cancer therapeutic modalities and intervention continues to evolve with the use of chemotherapy, molecular therapy, monoclonal antibodies including tumor targeting, checkpoint therapy antibody drug conjugates and the recent approval of target-specific autologous T-Cell therapy (CART). The next wave of immunotherapies includes technologies to adopt and enhance the natural anti-tumor biology of 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.
Recent advances in engineered autologous T-cell therapy (CART) has led to demonstrated, transformational anti-tumor activity. However, the complexity, cost and significant safety challenges of CART potentially impede its broad adoption. Unlike approved CART 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 are seen to have a significantly safer therapeutic profile, without the potential for cytokine release syndrome and neurotoxicity seen with CART. However, the NK therapy field has been hampered by inadequate manufacturing supply of highly active, tumor targeting cells.
The proprietary Artiva NK cell therapy platform utilizes cell expansion and activation technology developed and enhanced for over a decade by our corporate partners GC Labcell. Healthy donor, licensed umbilical cord blood (UCB) Units, with KIR B-haplotype and high affinity CD16 polymorphism are selected from U.S. cord blood banks. Each UCB is used to derive a NK cell master cell bank followed by a bioreactor-based large-scale NK cell expansion and activation 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 ensure long term stability, practical logistics, and ease of handling at the clinical site.
Artiva utilizes a proprietary CAR platform, optimized for use in NK cells, to enhance their therapeutic activity and tumor targeting capability. Multiple co-stimulatory domains are used in combination with tumor targeting motifs and co-expression of IL-15 for cytokine support of the therapeutic cells. Additionally, all CAR-NK products maintain high expression of the naturally high-affinity variant CD16, enabling dual targeting therapeutic approaches via monoclonal antibody combinations. Aritva is 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.