Spotlighting a Breakthrough in the Race to Treat Cancer

(DGIwire) – The human immune system has evolved over the course of 500 million years into a personalized and effective natural defense against disease. Which raises the question: Why doesn’t the immune system fight cancer? The answer is, it does, or tries to. But cancer uses tricks to hide from the immune system, shut down the body’s defenses and avoid the fight. Cancer immunotherapy is the approach that works to defeat the tricks, unmask cancer, unleash the immune system and restart the battle.

This eloquent summary of the state of immunotherapy is introduced in a recently published book: The Breakthrough: Immunotherapy and the Race to Cure Cancer by Charles Graeber. The book explores the extraordinary promise of a new approach to attacking a disease that has afflicted humanity since the dawn of time.

“The increasing spotlight on immuno-oncology—in popular books, newspapers, magazines and online—reveals the appeal this strategy has beyond the confines of the research lab and clinic,” says Gerrit Dispersyn, Dr.Med.Sc., CEO of Phio Pharmaceuticals. “There is much to find exciting about the promise of this field.”

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.

“The next chapters in the adventure story of immuno-oncology have yet to be written but they are sure to be exciting,” adds Dispersyn.