August 18, 2023
A $2.8 million grant from the National Cancer Institute will help researchers overcome challenges in using engineered T cells to treat glioblastoma.
Chimeric Antigen Receptor (CAR) T cell therapy is a form of immunotherapy that uses reengineered versions of a person's own immune cells to find and fight cancer cells. T cells are extracted from the patient, genetically modified and returned to the patient's bloodstream to seek and destroy remaining cancer cells. There are currently six approved CAR T therapies in the United States that target blood cancers. Despite many efforts, there are currently no CAR T therapies that have been developed and approved for solid tumors, which account for most cancers.
Typical treatment for glioblastoma is surgery, followed by chemotherapy and radiation. While treatment can prolong the patient’s life, it cannot eliminate the cancer. People with glioblastoma face a grim prognosis: The five-year survival rate is less than 7%. David Akhavan, MD, PhD, principal investigator and assistant professor in the Department of Radiation Oncology, has dedicated his scientific career to finding ways to better treat this disease.
One common challenge is T cell “exhaustion,” when engineered T cells lose their ability to identify and kill tumors after prolonged exposure to the tumor. Another problem is the tumor’s surrounding microenvironment, which hinders CAR T cells’ ability to penetrate the tumor.
“New treatments for glioblastoma are desperately needed,” Dr. Akhavan said. “To overcome the challenges we've faced, we plan to leverage nanotechnology.”
Supporting Dr. Akhavan is Stefan Bossmann, PhD, professor in the Department of Cancer Biology and an internationally recognized expert in nanotechnology as it relates to drug delivery and imaging.
Nano-scale devices are unique manufactured structures used at the tiniest scale. Nanotechnology can be used to develop new treatments for cancer. The team will look at whether employing nanotechnology will enhance CAR T cell’s effectiveness in treating solid tumors by addressing a specific receptor that blocks the engineered T cells’ ability to eradicate tumors.
The team has developed a platform technology to equip CAR T cells with nanocarriers, which will control the release and extend the life of the engineered cells once infused back into the patient. The goal is to ward off T cell exhaustion for up to three weeks, giving the treatment a larger window to eradicate cancer.
“Immunotherapy holds the promise of a potentially curative treatment for glioblastoma,” Dr. Akhavan said. “Collaborations such as ours are needed to bring different disciplines together to make progress against this terrible disease.”