A combination of three previously established therapies, detailed recently in PLOS One, has been demonstrated to significantly prolong the survival of mice with glioblastoma. The triple therapy, consisting of two distinct immunotherapies and targeted radiotherapy, was investigated by researchers at Johns Hopkins Kimmel Cancer Center (MD, USA).
“Traditionally, radiation is used as a definitive therapy to directly kill cancer cells,” commented Michael Lim of Johns Hopkins Medicine, one of the study authors. “But in this situation we’re using radiation as kind of kindling, to try to induce an immune response.”
Specifically, the tested combination consists of radiation therapy targeted at the tumor, an antibody therapy targeted at CTLA-4 on T cells and a therapy termed 4-1BB that stimulates the activation of antitumor T cells.
In animal studies, mice implanted with mouse-derived glioblastoma cells were demonstrated to survive for 67 days after receiving the triple therapy, compared with survival of 24 days for animals who only received the two immunotherapies. The study also described how half of the animals who were treated with the triple therapy survived for 100 days or more, while also seemingly being protected against further tumors upon injection of new cancer cells.
Charles Drake, also of Johns Hopkins Kimmel Cancer Center, explained how the immune system is not known to generate a memory when foreign cells are present in the body. “But the idea that this combination treatment was successful at generating immunological memory really suggests that we could do this in patients and generate some long-term responses.”
Lim postulates that once destroyed by radiation, dead tumor cells release proteins that aid in recognition of the tumor by the immune system. He also suggests that the radiation can be delivered a few days either side of the immunotherapies and still maintain the same effects.
The research will continue with the development of a variety of clinical trials to further test combination therapies against brain tumors.