Yale study unlocks potential of lupus-related antibody to target cold tumors

Yale scientists have discovered a promising way to trigger immune responses against certain tumors, using a lupus-related antibody that can slip, undetected, into "cold" tumors 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. By doing that, the antibody has significantly prolonged survival in brain tumor models by itself-without radiation or chemotherapy."

Dr. James Hansen, study's senior author, radiation oncology chief of Yale's Gamma Knife Program, and member of Yale Cancer Center

Cold tumors, sometimes called immune deserts, typically do not have many T cells so they don't respond well to cancer treatments, including immunotherapies. However, "hot tumors" 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 tumors," 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 tumor, 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.

Yale's Xiaoyong Chen joined Hansen as the study's first author. Other Yale authors include Xiangjun Tang, Ying Xie, Benedette Cuffari, Caroline Tang, Fei Cao, Xingchun Gao, Zhouqi Meng, Philip Noble, Melissa Young, Olivia Turk, Anupama Shirali, and Jiangbing Zhou. Researchers from UCLA and the Veterans Affairs Greater Los Angeles Healthcare System also contributed to this study.