Tri-specific NK cell Engagers (TriKEs) and Dual Targeting NK cell Engagers
The generation of Chimeric Antigen Receptor, or CAR, expressing T cells from monoclonal antibodies has represented an important step forward in cancer therapy. These therapies involve the genetic engineering of T cells to express either CARs, or T cell receptors, or TCRs, and are designed such that the modified T cells can recognize and destroy cancer cells. While a great deal of interest has recently been placed upon Chimeric Antigen Receptor T, or CAR-T, therapy, it has certain limitations for broad potential applicability because it can require an individual approach that is expensive, time consuming, and maybe difficult to apply on a large scale. We believe there is an unmet need for targeted off-the-shelf therapies that can be used on a stand-alone basis, augment the current monoclonal antibody therapeutics and be used in conjunction with more traditional cancer therapy.
To accomplish this goal, we have generated a pipeline of clinical and non-clinical product candidates consisting of tri-specific killer engagers, or TriKEs, and tetra-specific killer engagers, or TetraKEs, designed to target natural killer, or NK, cells and tumor cells forming] an immune synapse between the NK cell and the tumor cell thereby inducing NK cell activation at that site. NK cells mediate ADCC through the highly potent CD16 activating receptor.
We believe our product candidates have the potential to overcome some of the limitations of CAR-T therapy and other antibody therapies. Unlike full-length tri-specific antibodies, TriKEs and TetraKEs are small single-chain fusion proteins that bind the CD16 receptor of NK cells directly producing a more potent and lasting response as demonstrated by preclinical studies. An additional benefit that they may have is an attractive biodistribution as a consequence of their smaller size which is expected to be important in the treatment of solid tumors. In addition to these advantages, TriKEs and TetraKEs are designed to be non-immunogenic, have quick clearance properties and can be engineered quickly to target a variety of tumor antigens. We believe these attributes make them an ideal pharmaceutical platform for potentiated NK cell-based immunotherapies.