(iPSC-Derived NK & CAR-NK Cells)

Cytovia Therapeutics is developing off-the-shelf NK cell therapies to address some of the most challenging unmet medical needs in cancer. Our platform includes unedited iNK, gene-edited iNK, and gene-edited CAR-iNK cells. 

We engineer our cells through a combination of technologies designed to overcome previous hurdles to effective immunotherapy.

We use induced pluripotent stem cells (iPSCs) as starting material for our cell products. Discovered by 2012 Medicine Nobel Prize Professor Shinya Yamanaka (Kyoto University), iPSCs are derived from initially-mature cells that have been reprogrammed back into an immature stem cell state, where they have an unlimited ability to multiply and can be differentiated into any cell type. This facilitates highly-scalable and cost-effective production of a consistent product. 

The use of iPSCs allows us to optimize the design and improve the function and persistence of the cell product through gene-editing. We perform multiple edits on a single iPSC clone, which can then be selected and used as a new source of starting material. iPSC-derived approach also helps us avoid potential clinical-relevant genome abnormality issues introduced by gene-editing thanks to rigorous quality control testing on master cell bank of the edited single cell clone, which is difficult to apply to donor-derived starting material.

We edit our stem cells using TALEN® technology from Cellectis, allowing us to choose an optimal locus to cut DNA before either repairing it to “knock-in” edits that we want or disrupting it to “knock-out” genes we don’t want expressed. This precise targeting leads to homogeneous and predictable expression levels and allows for potentially more standardized manufacturing designed to increase safety and offer better therapeutic activity.

The addition of Chimeric Antigen Receptors, or CARs, into selected iPSCs gives the later manufactured CAR-iNK cells "GPS coordinates" for their targets by binding only to the desired tumor antigen(s) expressed on cancer cells. The Chimeric Antigen Receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. Through the selection of appropriate target antigens, these receptors can help guide NK cells to their targets. NK cells genetically modified with a CAR have demonstrated clinical activity against hematological cancers.

In preclinical studies, Cytovia iNK cells have shown cytotoxic anti-tumor activity that is enhanced when combined with our Flex-NK™ cell engager.