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 (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. CAR-T therapy can require an individual approach that is expensive, can be time consuming, and may be 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, can augment current monoclonal antibody therapeutics, and can 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, designed to target natural killer (NK) cells and tumor cells. TriKEs form an immune synapse between the NK cell and the tumor cell, thereby inducing NK cell activation at that site. NK cells mediate antibody dependent cellular cytotoxicity (ADCC) through the highly potent CD16 activating receptor. Also contained within the TriKE molecule is a human interleukin-15 (IL-15) crosslinker, which further enhances NK cell proliferation and persistence.
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 are small single-chain fusion proteins that bind the CD16 receptor of NK cells using nanobody technology, which has been shown in preclinical studies to produce a more potent and lasting response. Additionally, these product candidates may have an attractive biodistribution as a consequence of their smaller size – a factor that is expected to be important in the treatment of solid tumors. TriKEs are also designed to be non-immunogenic, have quick clearance properties, and can be engineered rapidly to target a variety of tumor antigens. We believe these attributes make them an ideal pharmaceutical platform for potentiated NK cell-based immunotherapies.