Research efforts may lead to the development of low-cost immunotherapy
BYU professor of microbiology and molecular biology Kim O'Neill works with students in his research lab.
Photo by BYU Photo
One person dies every 50 seconds in the U.S. from cancer, and an estimated 39% of people in the country will develop cancer during their lifetime. Survival rates have improved in recent decades from innovations and combinations of treatments, including surgery, chemotherapy, radiation, immunotherapy and biotechnology. Still, some cancers resist treatment or recur.
BYU preclinical research shows a promising new immunotechnology called MOTO-CAR that genetically engineers macrophages — immune cells that can enter solid tumors — to recognize cancer-associated markers, attack the tumor cells, and activate other immune cells with a memory to fight the cancer. Researchers hope it will eventually lead to treatments for difficult-to-cure cancers, including glioblastoma, triple-negative breast cancer and pancreatic cancer.
“Our unique MOTO-CAR technology is designed to convert the patient’s own immune system to recognize and fight the cancer,” said Kim O’Neill, a BYU professor of Microbiology and Molecular Biology. “We are hoping to make the treatment cost more affordable so that people can use it around the world. If successful, this technology may reduce the need for surgery, chemotherapy or radiation.”
BYU students have conducted MOTO-CAR studies for the last six years, many of whom received support from BYU’s Simmons Center for Cancer Research. To protect the patent process, the results have not yet been formally published. However, BYU patents have now been issued and transferred through a licensing agreement to Thunder Biotech, a research partner company founded by O’Neill in 2016. The researchers are now focused on transforming years of scientific discovery into practical solutions that can benefit patients and society.
O’Neill described the findings as very promising. In one in vitro study, researchers observed a 90% reduction in aggressive lung cancer cells within 24 hours. In another, a single treatment regimen was associated with a 46% reduction in tumor size in mice.
The MOTO-CAR technology is designed to convert the patient’s own immune system to recognize and fight the cancer.
Photo by BYU Photo
“Since 2018, we’ve been taking our BYU studies to independent companies for validation,” O’Neill said. “They don’t know our biotechnology, but they know what it does; we can change the receptors on the MOTO-CAR surfaces to bind to different targets on different cancer types, and we still get similar tumor reduction size in mice.”
How MOTO-CAR differs from other technologies and how it works
MOTO-CAR is being developed as an off-the-shelf treatment that could be selected after a biopsy. Unlike other therapies that require blood draws and personalized cell modification, this approach could make treatment more efficient and affordable.
MOTO-CAR builds on CAR T-cell therapy, which received its first FDA approval in 2017. CAR T-cell therapies have seen impressive success with blood cancers but have limited success in solid tumors. They can also be costly and require long-term patient monitoring.
Rather than modifying T cells, MOTO-CAR focuses on macrophages, which are the most abundant immune cells in solid tumors.
The MOTO-CAR therapeutic is packaged within a nanoparticle delivery system. This system is microscopic, with millions of nanoparticles being able to fit inside the size of a period on this page. The delivery system is designed to target Tumor-Associated Macrophages (TAMs) that surround and protect the tumor.
When the nanoparticles bind to TAM’s, they release the patented MOTO-CAR technology. The technology reprograms macrophages to attack and digest tumor cells while presenting tumor-specific antigens to the patient’s immune system. This is intended to trigger a broader immune response, recruiting additional immune cells to recognize, target and eliminate cancer throughout the body. The technology is designed to produce an immune memory.
As far as what the actual treatment will look like, the researchers envision a process in which a clinician would biopsy a tumor to identify the cancer type and biomarkers. The treatment team would then select a pre-engineered MOTO-CAR therapeutic. With appropriate approval, a clinician would administer the MOTO-CAR therapeutic, possibly through simple infusion.
The expected effects may include flu-like symptoms around day 3-4. By day 14-28, the immune system would hopefully be in full force attacking the tumor.
The future of MOTO-CAR cancer research
The research remains preclinical, and further work and funding are needed before human clinical trials can begin. Thunder Biotech would need to partner with a pharmaceutical company or other financial sources to help conduct those trials and evaluate the treatment’s safety and effectiveness. With FDA approval, MOTO-CAR therapy could eventually become a cancer-treatment option.
O’Neill envisions the cancer treatment being cost-effective compared to current treatments.
“Scientific discoveries do not always translate seamlessly from the laboratory to animal models and ultimately to human patients,” O’Neill said. “While the path from research to clinical application is often challenging, my confidence in this work remains strong. I believe the inspiration behind these scientific concepts came from a higher source, and the remarkable opportunities and outcomes we have witnessed along the way have only strengthened that conviction.”
Media Contact: Todd Hollingshead
Tags
Life Sciences
