New cancer vaccines
Researchers in the Center for Neuro-Oncology are launching attacks on glioblastomas from a new angle – by turning the patient’s immune system against the cancer cells. Where targeted chemotherapy uses drugs to disable proteins that cancer cells need to grow, immunotherapy drugs stimulate the patient’s immune system to recognize and kill cancer cells.
In November 2014,
David Reardon, MD, who leads the immunotherapy effort for brain tumors, reported that a new cancer vaccine, rindopepimut, showed promise in a clinical trial of patients whose glioblastoma cells contain a particular gene mutation.
Cancer vaccines are a form of immunotherapy that have been studied and tested for many years with some success. The vaccines are often made from an individual patient’s tumor cells, or parts of them, processed in the laboratory, and returned to the patient to stimulate a strong immune response.
Rindopepimut, given along with the anti-angiogenic drug Avastin, significantly improved the survival of patients whose tumors carried the mutation known as EGFRvIII, which is found in about one-third of glioblastoma tumors. It was the first randomized clinical trial of immunotherapy to show a survival benefit in glioblastoma.
Reardon is also leading a study of NeoVax, a "personalized neoantigen cancer vaccine," which is already in testing for melanoma at Dana-Farber.
The NeoVax vaccine is made with "tumor-specific antigens" that correspond to the unique set of such antigens on the surface of an individual patient’s tumor cells. It’s been shown that these highly specific antigens can stimulate a potent, focused immune response.
If the vaccine proves effective, it will be combined in further trials with immune checkpoint blockers that target proteins PD-1 and PD-L1 to remove the brakes that cancer uses to suppress an immune response. New drugs that attack these checkpoints have had dramatic and long-lasting results in some patients with advanced metastatic melanoma.
Dana-Farber researchers are also evaluating several other immunotherapy approaches for brain cancer in the lab and the clinic.
Reprogramming immune cells
In a related project currently being tested in animal models, David Reardon, MD, of Dana-Farber, in collaboration with David Mooney, PhD, of the Wyss Institute, is optimizing an implantable "matrix" of biomaterials designed to reprogram immune cells in the patient’s body to generate a potent immune attack on glioblastoma tumors.