Brain tumor organoids accurately model patient response to CAR T cell therapy

 For the first time, researchers used lab-grown organoids created from tumors of individuals with glioblastoma (GBM) to accurately model a patient's response to CAR T cell therapy in real time. The organoid's response to therapy mirrored the response of the actual tumor in the patient's brain. That is, if the tumor-derived organoid shrunk after treatment, so did the patient's actual tumor, according to new research from the Perelman School of Medicine at the University of Pennsylvania, published in Cell Stem Cell.

"It's hard to measure how a patient with GBM responds to treatment because we can't regularly biopsy the brain, and it can be difficult to discern tumor growth from treatment-related inflammation on MRI imaging," said Hongjun Song, PhD, the Perelman Professor of Neuroscience and co-senior author of the research. "These organoids reflect what is happening in an individual's brain with great accuracy, and we hope that they can be used in the future to 'get to know' each patient's distinctly complicated tumor and quickly determine which therapies would be most effective for them for personalized medicine."

GBM is the most common -- and most aggressive -- type of cancerous brain tumor in adults. Individuals with GBM usually can expect to live just 12-18 months following their diagnosis. Despite decades of research, there is no known cure for GBM, and approved treatments -- such as surgery, radiation, and chemotherapy -- have limited effect in prolonging life expectancy.

A treatment called CAR T cell therapy reprograms a patient's T cells to find and destroy a specific type of cancer cell in the body. While this therapy is FDA approved to fight several blood cancers, researchers have struggled to engineer cells to successfully seek out and kill solid tumors, like in GBM. Recent research suggests that CAR T cell therapy that targets two brain tumor-associated proteins -- rather than one -- may be a promising strategy for reducing solid tumor growth in patients with recurrent glioblastoma.

"One of the reasons why GBM is so difficult to treat is because the tumors are incredibly complicated, made up of several different types of cancer cells, immune cells, blood vessels, and other tissue," said study co-senior author, Guo-li Ming, MD, PhD, the Perelman Professor of Neuroscience and Associate Director of Institute for Regenerative Medicine "By growing the organoid from tiny pieces of a patient's actual tumor rather than one type of cancer cell, we can mirror how the tumor exists in the patient, as well as the 'micro-environment' in which it grows, a major limitation of other models of GBM."

The first line of treatment for GBM is surgery to remove as much of the tumor as possible. For this study, researchers created organoids from the tumors of six patients with recurrent glioblastoma participating in a Phase I clinical trial for a dual-target CAR T cell therapy. It can take months to grow enough cancer cells in the lab to test treatments on, but an organoid can be generated in 2-3 weeks, while the individuals recover from surgery and before they can begin CAR T cell therapy.

Source: ScienceDaily