An Amazing Year for a Weapon Against Cancer

(DGIwire) – Immuno-oncology continues to prove its worth as an extraordinary research area in cancer care. Finding ways to customize the human immune system to power-up the battle against cancer has led to a wide range of breakthroughs so far, and the year 2018 was no exception. In a recent recap of the top immuno-oncology stories of the year, highlighted several newsworthy tidbits. These included everything from the elimination of cancer in mice whose tumors came from cells of people with advanced pancreatic cancer, to the identification of new biomarkers in the blood that could be used to identify patients most likely to respond to certain immunotherapies.

“Every new year brings a slew of exciting new advances in immuno-oncology,” says Gerrit Dispersyn, Dr.Med.Sc., CEO of Phio Pharmaceuticals. “There is no reason to believe that the pace will slow down anytime soon, and work being done in the lab today supports this notion.”

Phio is at the forefront of these efforts in light of its development of a proprietary therapeutic platform technology called “self-delivering” RNAi or sd-rxRNA®. RNAi is a naturally occurring process by which short double-stranded RNAs interfere with the expression of targeted genes. The development of therapeutics based on RNAi technology takes advantage of this phenomenon and allows for the reduction of the expression of particular genes within living cells. RNAi offers a novel approach to the drug development process because RNAi compounds can be designed to target any one of the thousands of human genes, many of which are undruggable by other modalities. Scientists at Phio have used an approach to delivery in which drug-like properties are built directly into the RNAi compound itself. These novel compounds are termed sd-rxRNA. The therapeutic and built-in delivery properties of sd-rxRNA compounds provide for a powerful method to harness the immune system to attack cancer.

Central to the immune system’s activity against cancer, are the immune-effector cells, such as tumor infiltrating lymphocytes (TILs). Therefore, emerging therapies are being developed for boosting these cells through the use of the adoptive cell therapy (ACT) method. This is a process by which immune cells are obtained from a patient or cell bank, expanded and treated ex vivo, then reinfused into a patient. Given that sd-rxRNA compounds are highly amenable to local delivery applications, the addition of a pre-treatment of immune cells with sd-rxRNA compounds can be used to silence one or more immuno-suppressive genes (such as PD-1 and other checkpoints), thereby weaponizing the immune cells, boosting their ability to detect and destroy tumor cells.

Among a wide range of other work being done in this area, research has been conducted evaluating sd-rxRNA compounds targeting immune checkpoints and/or other immuno-suppressive targets in combination with recombinant T-cell receptors to develop modified T-cells with enhanced efficacy for the treatment of solid tumors. Results demonstrate a significant reduction of PD-1 surface levels in activated T-cells (non-engineered) treated with sd-rxRNA and a reduction of PD-1 surface levels in T-cells transduced with T-cell receptors and treated with sd-rxRNA.

“What will the future of immuno-oncology bring? No one has a crystal ball, but it’s safe to predict that more important results to benefit the field are on the way,” adds Dispersyn.