Guidance and Navigation Control (GNC) molecules are multi-specific cell engager proteins.  GNC in the oncology therapeutics class bind to cancer cells and to immune cells and stimulate the immune cell cancer killing activity.  By design, each GNC molecule is multi-function. In the process of killing, the GNC is designed to educate and empower the T cells to be more effective at killing cancer.

The GNC-039, octavalent, tetra-specific T cell engager is designed to target EGFRvIII in certain solid tumors.  This molecule is the second tetra-specific therapeutic antibody tested in human trials and represents the concept of Guidance and Navigation Control.

The GNC-039 molecule can bind CD3 and EGFR-vIII to redirect T cell cytotoxicity toward specified cancer indication defined by EGFR-vIII expression. The molecule can also redirect T cell cytotoxicity toward PDL1 high expressing cells, representing its potential to convert cancer cell adaptive resistance into drug sensitivity. In tumor with heterogenous expression of EGFR-vIII this mechanism may allow the targeting of proximal cancer cells in a drug dependent fashion, in addition to the targeting of local immunosuppressive cells expressing PDL1.  The GNC-039 can also engage 41-BB in a non-cytolytic fashion, transducing an educational signal to T cells that leads to increased functionality throughout a serial dosing cycle of therapy.  

GNC-039 is currently being evaluated as a single agent in clinical trials enrolling patients with a Glioblastoma and other EGFR-vIII+ solid tumor indications.