Glioblastoma multiforme (GBM), a devastating type of brain cancer, has been in the news again with Senator John McCain’s recent diagnosis. It is notoriously aggressive, growing rapidly and often defying treatment with surgery, radiation and chemotherapy. Tumors can be removed by surgery, but they nearly always come back. By most estimates, half the patients with this diagnosis will succumb to it in 15 to 18 months, and only five or 10 percent will be living in five years.
Scientists supported by Stand Up To Cancer are working to extend some of the latest insights in cancer, including immunotherapy, into this fast-moving and deadly disease. They are also seeking better treatments for other forms of cancer of the brain and central nervous system in adults, children and infants.
Here is a snapshot of this promising research:
Marcela Maus, MD, PhD, director of cellular immunotherapy at the Massachusetts General Hospital Cancer Center, received an immuno-oncology Innovative Research Grant (IRG) from SU2C, with support from Bristol-Myers Squibb (BMS) Company, for her research on the use of chimeric antigen receptor (CAR) T cells against GBM. CAR T cells have been used very successfully to treat leukemia and other blood cancers and are now being investigated for use against solid tumors. In earlier work, Dr. Maus and her team were able to get the CAR T cells into the brain without the side effects that are sometimes encountered with CAR T-cell therapy. However, the tumors were able to defend themselves against the CAR T cells, and no obvious shrinkage of the tumors occurred in the first group of patients treated.
“Basically we need to turn up the potency in solid tumors,” Dr. Maus told the Stat Plus newsletter.
With the support of the SU2C Innovative Research Grant, Dr. Maus and her lab are now working to develop a second generation of CAR T cells that target cancer cells with a combination of specific gene mutations found in many glioblastomas. She also hopes to modulate the tumor microenvironment to make it less immunosuppressive so as to give the T cells a better chance to work.
At Baylor College of Medicine in Houston, Meenakshi Hegde, MD, who also received an IRG supported by a grant from BMS, is working to develop CAR T cells that specifically recognize and target the human epidermal growth factor receptor 2 (HER2), a protein that is associated with glioblastoma. Dr. Hegde and members of her lab are developing a new way to give T cells the ability to overcome inhibitory pathways to enhance their effectiveness against glioblastoma.
“This study has the potential to dramatically improve outcomes for glioblastoma patients and advance information leading to future standards in brain tumor immunotherapy,” Hegde said.
In Canada, the SU2C Canada Cancer Stem Cell Dream Team is investigating brain tumor stem cells, a subset of cells within the tumor that are responsible for driving its growth and relapse. The team is led by Peter Dirks, MD, PhD, at the Hospital for Sick Children in Toronto, and Samuel Weiss, PhD, director of the Hotchkiss Brain Institute at the University of Calgary. The team is analyzing samples from tumors to try to identify genes that are specific to the tumor stem cells. Identifying the genes that drive their growth would provide a target for therapy. In addition to studying glioblastomas in adults, the team is also analyzing ependymomas in children and infants.
“The question is, how do we apply what we know about normal neural stem cells and get a deeper understanding of abnormal stem cells (in brain tumors)? That’s what this grant will really allow us to do,” Dr. Weiss told the Toronto Globe and Mail.