Flex-NK™ Cell Engagers
Cytovia has developed Flex-NK™ cell engagers to redirect and trigger the killing activity of NK cells towards tumor targets. These next-generation multispecific antibodies can be used as monotherapy in patients with good NK status. In patients with impaired NK status, we can administer either our unedited or gene-edited iNK cells to further enhance the potential therapeutic activity.
Our Flex-NK™ cell engagers are built on a proprietary tetravalent, multifunctional format, allowing for higher avidity and improved affinity. Specific mutations enable consistent proper pairing of antibody heavy and light chains. A flexible linker facilitates simultaneous binding to multiple antigens, even if they are expressed in different cells.
One pair of the fragment antigen-binding (F(ab’)2 fragment) of the antibodies targets tumor antigens expressed on the cancer cells, while the second pair simultaneously binds to NKp46 to engage NK cells. NKp46 mediates NK-cell lysis in both autologous and allogeneic cells and shows sustained expression on NK cells in the tumor microenvironment, as opposed to other activating receptors - such as NKG2D, NKp30, CD16, NKp44 – which are frequently downregulated. When a tumor cell is bound by the Flex-NK™ cell engager and the NK cell is bound by NKp46, the NK cell is empowered to recognize and kill the tumor target.
The tail, or Fc region, of the antibody increases its half life and cytotoxicity. It can be mutated to decrease or optimized to enhance specific binding to CD16a, an activating receptor on NK cells. CD16a is also expressed on macrophages and monocytes.
The patented Flex™ platform scaffold provides the opportunity to develop product candidates against any tumor antigen beyond the current nominated GPC3 and CD38 targets to allow for development of multiple drug candidates for Cytovia and its potential corporate partners. The platform has been validated by academic investigations led by our scientific co-founder and Global Head of Antibody R&D Dr. Jean Kadouche. Cytovia’s R&D labs continue to further development of this platform.