Combating Cancer - Oncolytic Virus Super-Activates the Immune System to Destroy Cancer
MUSC’s Dr. Eric Bartee and Systems Oncology, LLC, a company that translates scientific research into clinical therapies, are partnering to eradicate cancer. MUSC Foundation for Research Development and Systems Oncology reached a licensing agreement for an armed oncolytic viral therapy developed by Dr. Bartee in 2017, and then the parties entered into a sponsored research agreement to develop the next generation dual armed oncolytic virus.
The immune system is the body’s own natural defense system, continually protecting against infection and disease. When the body develops cancer, abnormal antigens are produced that alert the immune system something is wrong. Ideally the immune system attacks at full speed until the threat is eliminated, and then puts on the “brakes” to avoid harming normal cells. These “brakes” in the immune system are known as checkpoint pathways. Cancer hijacks these pathways, forcing the immune system “brakes” to be pressed early to effectively trick the immune system into protecting cancer cells.
Oncolytic therapy is an emerging immunotherapy treatment, which uses viruses that preferentially infect and kill cancer cells.The virus is injected into the tumor, and as the cells die they release antigens that trigger the immune system to target the cancer cells in the body that have the same antigens. The initial induction of the immune response is robust, but subsequent efficacy is often inhibited in part through PD-1/PD-L1, key proteins in a checkpoint pathway which put on the “brakes” too early.
Dr. Eric Bartee at MUSC is paving the way to generate an oncolytic virus that safely and effectively eradicates cancer without being slowed down by this checkpoint pathway. Dr. Bartee’s lab studies “myxoma”, a pathogenic virus related to smallpox which causes the infamous and often fatal “myxomatosis” disease in rabbits. Although myxoma is not known to cause infections in any other species, and it does not replicate in human cells, it has been discovered as a cancer selective oncolytic virus. Dr. Bartee genetically endowed the ability for myxoma to secrete a protein which acts as a PD-1/PD-L1 pathway inhibitor. A unique advantage of Dr. Bartee’s original armed myxoma is that since it stays within the tumor, checkpoint inhibition is focused on the tumor microenvironment unlike current FDA approved systemic checkpoint therapies. This provides the immune system the green light at the tumor by lifting the “brakes” while allowing normal checkpoint function in other areas to reduce treatment side effects.
The phenomenal results of this genetically engineered virus were published in Cancer Research in 2017, which showed more effective control of tumors in mice compared to a treatment that combined a PD-1 checkpoint inhibitor and native myxoma virus.Although promising, there are still hurdles to move this therapy from an animal model to humans. Significant barriers include reaching large-scale production of clinical-grade virus and translating the preclinical studies to humans.
During negotiating the license agreement, MUSC Foundation for Research Development and Systems Oncology determined additional academic research was needed, which System Oncology sponsored in Dr. Bartee’s lab. When asked about the partnership, FRD Associate Director, Scott Davis said, “Systems Oncology has been an ideal partner. When they came to us, we knew additional research was needed. They have stepped up to the plate by not only sponsoring work in Dr. Bartee’s lab, but contributing their own ideas which have been critical for project development. We are really excited to see how this research continues to move forward”.
Dr. Spyro Mousses, Systems Oncology’s CEO said, “This collaboration has been incredibly productive. By sponsoring research at MUSC, and effectively joining forces with Dr. Bartee and his team, we were able to achieve a significant breakthrough discovery. Specifically, using Dr. Bartee’s cutting-edge research as a starting point for the collaboration, we jointly leveraged additional novel insights into cancer biology to engineer and test next generation dual armed oncolytic viruses. These new agents were designed to locally kill cancer cells while simultaneously expressing two kinds of engineered proteins that together super-activate and train immune cells to more effectively recognize and kill cancer cells throughout the body. The safety and efficacy profiles from the lead construct were better than we could ever hope for. This new approach represents a paradigm shift in cancer immunotherapy, and the in vivo results suggest that this new agent has tremendous potential to improve outcomes for cancer patients.We are absolutely thrilled with what we were collectively able to achieve through this collaboration, and we are now focused on advancing this important discovery into the clinic in the next year or so.”