Researchers at the Fralin Biomedical Research Institute at VTC have developed an experimental oral therapy that protected mice from otherwise harmful radiation exposure while preserving radiation's ability to destroy cancer cells, a finding that could ultimately improve cancer treatment and strengthen preparedness for radiological emergencies.
Published in the September issue of Cancer Letters , the study describes an investigational therapy called XOlacta that packages a therapeutic peptide known as alpha-CT11 inside naturally occurring milk-derived extracellular vesicles, which are tiny, naturally occurring particles that cells use to transport biological molecules. The vesicles protect the peptide as it passes through the digestive system, allowing the treatment to be administered orally rather than by injection.
"There are currently no treatments that protect the body from the widespread effects of high-dose radiation exposure," said Robert Gourdie, the Heywood Fralin Professor at the Fralin Biomedical Research Institute and the study's senior author. "Our goal was to develop a therapy that protects the organs most vulnerable to radiation injury while preserving radiation's ability to treat cancer."
Radiation therapy is used to treat approximately half of all cancer patients, but damage to healthy tissues can limit the amount of radiation physicians can safely deliver. Outside the clinic, accidental or intentional radiation exposure such as during a nuclear attack are significant public health concerns, and presently there are no FDA-approved medical countermeasures available for severe whole-body exposure.
In the study, mice receiving a lethal dose of whole-body radiation followed one hour later by a single oral dose of the therapy achieved a 42 percent, 30-day survival rate. By comparison, untreated mice did not survive the 30-day study period. The treatment also remained effective when administration was delayed for 24 hours after radiation exposure.
The researchers found that the therapy reduced damage to the small intestine and bone marrow — two of the tissues most vulnerable to radiation injury. Imaging studies also showed that the milk-derived vesicles preferentially accumulated in radiation-damaged tissues, including in the brain, gut and bone marrow, potentially concentrating the therapy where it was needed most.
Equally important, the treatment did not diminish radiation's effectiveness against tumors. In a mouse model of glioma brain cancer, the therapy protected healthy tissues while preserving radiation's ability to suppress tumor growth.
"One of the biggest challenges has always been protecting healthy tissue without protecting the cancer," said first author Spencer Marsh, a research scientist in Gourdie's laboratory. "Our findings suggest it may be possible to reduce many of the side-effects patients experience during radiation therapy while maintaining the treatment's effectiveness against tumors."
The oral delivery system offers several practical advantages over existing approaches. Because the therapy is stable at room temperature for a year or more, it could potentially be stored in homes, hospitals, on warfighters, and in emergency stockpiles, and administered quickly without specialized medical equipment. The investigators say the work remains in the preclinical stage, but development is advancing.
Independent studies conducted by contract research organization Lovelace Biomedical have reproduced the team's mouse findings, and the therapy is now progressing through additional safety and large-animal studies under the U.S. Food and Drug Administration's Animal Rule, a regulatory pathway for medical countermeasures that cannot be tested for efficacy in humans because of ethical considerations.
"Beyond the implications for strategic emergency preparedness, we believe this approach has the potential to improve the experience of cancer patients receiving radiation therapy," Gourdie said. "If we can reduce damage to healthy tissues without reducing the treatment's effectiveness against tumors, we may ultimately help patients better tolerate radiation and enable more effective treatment."
The multidisciplinary research team also included Claire Beard, Ruhul Amin, and Zhi Sheng of the Fralin Biomedical Research Institute; Mark Bannon and Rachel Letteri of the University of Virginia; and Ilektra Athanasiadi of the Virginia-Maryland College of Veterinary Medicine at Virginia Tech.
Gourdie and Marsh are officers in Tiny Cargo Co. , which is developing the technology described in the study in Roanoke, Virginia. Gourdie also co-founded Xequel Bio, a company developing related therapeutic peptides for wound healing. Virginia Tech, the Medical University of South Carolina, and Gourdie are associated with patents related to the peptide and milk-derived extracellular vesicle technologies used in this research. Gourdie is also a member of the Department of Biomedical Engineering of the Virginia Tech College of Engineering and Virginia Tech Carilion School of Medicine.
The research was supported by the National Institutes of Health, the National Science Foundation, the National Cancer Institute, the Red Gates Foundation, The Fralin Family, and the Fralin Biomedical Research Institute.
