Proprietary Technology Derived From An Oncolytic Virus
Targeted Immuno-oncology Therapeutic, Program I
We have developed a novel Immuno-Oncology platform technology that selectively activates the cancer immune system (natural killer (NK) cells, dendritic cells (DC), CD8 T cells, memory T cells) to target, infiltrate and destroy specific tumor types, without activating unrelated immune elements, which can cause immunotoxic side effects.
Our technology can be engineered to safely attack numerous different tumor types. Our first two indications are ovarian cancer and small cell lung cancer.
Our biologic therapeutic is a bi-specific multimeric viral glycoprotein and tumor associated antigen complex (VGP/TAA). The VGP is derived from the alphavirus, which has demonstrated promising tumor killing (oncolytic) potential.
The alphavirus has been shown to be efficacious in retarding xenograft tumor growth and prolonging survival, although it is not curative.
An engineered alpha viral vector (AV) expressing a tumor specific antigen (TAA) was shown, in a syngeneic mouse tumor model, to mediate regression of tumor growth and to inhibit metastasis through CD8+ T cell infiltration.
Tumor-specific CD8+ memory T cells were also observed in surviving mice more than 60 days after treatment.
Additionally, mice were immune to recurrence when the tumor was reintroduced into the animal even after clearance of the viral vector.
This immunity extended to tumors reintroduced that no longer expressed the tumor specific antigen, indicating that the immune system had become targeted to additional tumor antigens, which could prevent resistance.
Mechanism of Action
1. VGP targets TAA to DC via the receptor DC-SIGN, resulting in activation of TAA-specific CD8 T cells that can recognize and kill tumor cells and can form lasting memory against tumor recurrence.
2. VGP binding signals to DC to activate NK cells to attack tumor cells.
3. VGP binds to tumor cells directly through the overexpressed laminin receptor, resulting in tumor cell damage and increased antigenicity.
4. Dying tumor cells release additional antigens which are taken up by DC to activate other tumor-specific CD8 T cells for a broader immune response.