Yale scientists have discovered a promising way to trigger immune responses against certain tumours, using a lupus-related antibody that can slip, undetected, into "cold" tumours and flip on an immune response that has been turned off by cancer. The research, published in Science Signaling on March 25, offers new findings that could help improve therapies for glioblastoma and other aggressive cancers that are difficult to treat.

"It turns out when this antibody gets into the cell's cytoplasm [the liquid material inside the cell, excluding the nucleus] and it binds to RNA, it causes this thing called a pattern recognition receptor to wake up and say, 'This isn't supposed to be here,' which triggers an immune reaction," said the study's senior author Dr. James Hansen, radiation oncology chief of Yale's Gamma Knife Program, and member of Yale Cancer Center. "By doing that, the antibody has significantly prolonged survival in brain tumour models by itself -- without radiation or chemotherapy."

Cold tumours, sometimes called immune deserts, typically do not have many T cells so they don't respond well to cancer treatments, including immunotherapies. However, "hot tumours" typically do respond because they have immune cells, even though they are temporarily disabled by cancer.

"We're excited about this new way to engage the immune system to treat brain tumours," Hansen said. "Equally exciting is the discovery that this lupus antibody delivers genes to cells without needing any help from a virus, meaning it could be used to transform gene therapy strategies."

The researchers confirmed in lab studies that the antibody did not work in tissue that lacked functional immune cells. If the immune cells functioned properly, the autoantibody could carry and deliver functional RNA into tumour, brain, and muscle tissue. They hope the findings lead to improved strategies for non-viral gene delivery (use of physical forces to deliver genetic material into a cell) and immunotherapy treatment.