UCLA researchers have developed a promising new brain-cancer treatment that offers hope for a disease that is especially difficult to treat.
Robert Prins, PhD, and Linda Liau, MD, of the UCLA Jonsson Comprehensive Cancer Center, led a study to test an immunotherapeutic approach to treating glioblastoma. Also called grade IV astrocytoma, this condition is currently incurable with standard therapies. Treatment involves surgically removing the large tumor mass, followed by external beam radiation and chemotherapy.
Dr. Prins explains that patients diagnosed with glioblastoma typically have a prognosis of about 12-to-18 months — an outlook that hasn't changed in 30 years. "Innovative treatment options are desperately needed for this patient population," Dr. Prins says.
Discovering a breakthrough
Glioblastoma, according to the American Brain Tumor Association, is an invasive tumor that spreads too many different cells throughout brain tissue. This makes it impossible to fully remove in surgery, leading to recurrence every time.
Many tumors, such as melanoma and breast cancer, express well-characterized antigens that can be targeted by the immune system to kill the cancer cells. Unfortunately, that advantage does not exist for brain tumors. "T-cells don't usually go to the brain," says Dr. Liau. "We don't want our brains to be attacked by autoimmune disease, but when you have a brain tumor, that makes it difficult to induce an immunoresponse."
Linda Liau, MD
Adoptive cell transfer
The first step in their research was to use a demethylating agent called "decitabine" to upregulate antigens in the brain tumor and find a potential target. What they found was NY-ESO-1, a cancer testes antigen that, for years, has been successfully targeted in treatments for other forms of cancer.
Dr. Prins and Dr. Liau then completed a process called "adoptive cell transfer," in which they extracted T-lymphocytes from normal human peripheral blood and reprogrammed them with a T-cell receptor that targets NY-ESO-1.
"T-cells are able to move across the brain to hone in on the tumors as long as the tumor cells express the target," Dr. Liau says.
The perfect balance
The breakthrough is in the combination of decitabine to upregulate the tumor antigen followed by adoptive cell transfer and then an injection of the modified T-cells back into the body. So far, this method has shown promising laboratory results using mice.
"Immunotherapy is ideally suited to target isolated pockets of infiltrating tumor cells in the brain," Dr. Prins explains. Glioblastoma is invasive, and the modified T-cells are able to seek out and attack these pockets of tumor cells that can't be surgically removed.
In the study, this new brain-cancer treatment led to longer survival in all of the treated animals and cure in almost half.
Dr. Liau and Dr. Prins plan to continue their research in preclinical studies using patient-derived xenografts. That would be followed by clinical trials with patients.
Immunotherapy research is an exciting field that is expected to be one of the most promising avenues for cancer treatment in the near future. And through this avenue, medical researchers have a unique opportunity to gain the experience of scientists at the university, as well as medical experts in the David Geffen School of Medicine at UCLA.
By Patricia Chaney
