Will the ‘Immunotherapy Explosion’ Continue?

(DGIwire) – The field of immunotherapy—in which a patient’s immune system is made to fight against cancer cells—is exploding. This opinion was recently expressed by Dr. James Allison, the co-recipient of the 2018 Nobel Prize in Medicine, in Cancer Research Analyst, the official blog of the American Association for Cancer Research. For the first time, Allison wrote, the field of medicine has several potentially curative treatments for cancer, with some patients remaining cancer-free a decade or more after treatment. Over time, he added, cancer immunotherapy will continue its evolution in ways that will greatly improve patients’ responses to treatment.

“The increasingly rapid pace of achievements within the field of immuno-oncology is certainly encouraging,” says Geert Cauwenbergh, Dr.Med.Sc., CEO of Phio Pharmaceuticals. “Work being conducted in the laboratory today points toward improved therapies in the coming years.”

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.

“This is the most exciting era to be working in cancer research—and ongoing work will undoubtedly continue to build up the state of the science,” Cauwenbergh adds.