Triple Therapy Revs Up Immune System against Glioblastoma

A triple therapy for glioblastoma, including two types of immunotherapy and targeted radiation, has significantly prolonged the survival of mice with these brain cancers, according to a new report by scientists at the Johns Hopkins Kimmel Cancer Center. Mice with implanted, mouse-derived glioblastoma cells lived an average of 67 days after the triple therapy, compared with mice that lasted 24 days when they received only the two immunotherapies. Half of the mice who received the triple therapy lived 100 days or more and were protected against further tumors when new cancer cells were re-injected under the animals' skins. The combination treatment described in an open-access article published on July 11, 2014 in PLOS ONE consists of highly focused radiation therapy targeted specifically to the tumor and strategies that lift the brakes and activate the body's immune system, allowing anti-cancer drugs to attack the tumor. One of the immunotherapies is an antibody that binds to and blocks an immune checkpoint molecule on T cells called CTLA-4, allowing the T-cells to infiltrate and fight tumor cells. The second immunotherapy, known as 4-1BB, supplies a positive "go" signal, stimulating anti-tumor T cells. None of the treatments are new, but were used by the Johns Hopkins team to demonstrate the value of combining treatments that augment the immune response against glioblastomas, the most common brain tumors in human adults. The prognosis is generally poor, even with early treatment. "We're trying to find that optimal balance between pushing and pulling the immune system to kill cancer," said Charles Drake, M.D., Ph.D., an associate professor of oncology, immunology, and urology, and medical oncologist at the Johns Hopkins Kimmel Cancer Center.
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