The BioEclipse Approach
The pioneering work underway at BioEclipse Therapeutics approaches cancer immunotherapy from not just one, but several directions. We believe that to defeat cancer requires a drug with multiple mechanisms of action (MOA) that work synergistically and systemically to target and kill cancer cells all over the body, and at the same time, create a durable immune response that prepares the patient’s body to fight relapse and recurrence.
With our lead drug candidate, CRX100, we have used an intellectual property portfolio, developed by the company’s founders and exclusively licensed from Stanford University, to create a first-in-class immunotherapy that pairs the power of an oncolytic virus with the tumor-locating ability of cytokine-induced killer (CIK) cells. What is truly novel, is how this multi-modal therapy overcomes limitations that, until now, have hobbled the efficacy of cellular and oncolytic viral therapies.
How CIK Cells and Oncolytic Viruses Work Together to Kill Tumors
Patient-derived killer cells are treated ex-vivo with cytokines to create activated CIK cells, which are innate immune cells programmed to seek out, find and then kill cancer cells. The CIK cells are then infected with vvDD (vaccinia virus, double deletion). The virus hides inside the CIK cells until reaching the cancer cell, where the virus harnesses the cancer cell’s RAS oncogene pathway to explode and kill the cancer cell.
The antitumor effect of the combination of cytokine-induced killer (CIK) cells and attenuated vaccinia virus show that our CIK cells carry the oncolytic virus to the tumor bed in about 48-72 hours, after which a rapid burst of viral replication kills the tumor cells. When the virus is carried by CIK cells, it can reach tumors away from the vasculature. This produces more uniform distribution of viral infection within the tumor, which contributes to sustained viral gene expression and increased tumor destruction in-vivo.
Studies have demonstrated that there is a synergy between the cytotoxic effect of CIK cells and the oncolytic effect of the virus against tumor cells. The key attributes of this synergy are the protection of the virus by the CIK cells from immune system destruction, and the ability of the CIK cells to activate the immune response in the tumor microenvironment, thereby increasing the potency CRX100 significantly compared to using cells or virus alone.