OT-1 is developed to treat pancreatic ductal adenocarcinoma and prevent the potential liver metastasis, a lethal malignancy with the lowest 5-year patient survival of all tumor type routinely tracked (~6%). OT-1 delivers mRNA encoding a TRAP protein to the cells in the tumor site. The expression product of mRNA will be secreted by the transfected cells and diffuse throughout the tumor environment, capturing the CXCL12 with nanomolar binding affinity. CXCL12 is then TRAPPED and its function as the chemoattractant for regulatory T cells and myeloid-derived suppressor cells is abolished. These two cells are major players in suppressive tumor immune microenvironment. This approach could greatly enhance the efficacy of immunotherapy.
OT-2 is designed to deliver mRNA encoding TRAP protein targeting PD-1 to the cells in the tumor site. The PD-1/PD-L1 ligation plays an important role in the immune suppression as a mechanism of action for the cancer cell to evade immune surveillance. The expressed TRAP protein secreted by the transfected cells shows a picomolar binding affinity toward PD-1, a magnitude higher than that of Nivolumab, which is a clinically approved anti-PD-1 antibody. Once PD-1 is TRAPPED, its ligation with its receptor, PD-L1, is blocked, and therefore the immune suppression is reversed. Cancer cells will then be eradicated by the immune system.
OT-3 is designed to deliver mRNA encoding a TRAP protein (patent pending) to the tumor site. This particular TRAP protein secreted by the transfected cells capture a cytokine and the trapping of such cytokine could substantially modulate and improve the tumor immune microenvironment, resulting in elevated innate and adaptive immune response against the tumor cells.
OT-4 is a polymer-based self-assembly system that is designed to deliver siRNA against Kras mutant (G12D) to the cancer cells, which comprises 17% of KRAS-mutated lung adenocarcinoma. The siRNA targeting mutant KRAS could effectively distinguish mutated KRAS from normal KRAS and therefore reduce the off-target effect. OT-4 could knock down the expression of mutation Kras protein and stop the proliferation of cancer cells, offering a cure to these undruggable targets.