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Yale Researchers Unveil New Approach to Activate Immunity Against Tumors

A team of scientists from Yale University has made significant strides in stimulating immune responses against certain tumors by utilizing an antibody associated with lupus. This antibody has the unique ability to infiltrate “cold” tumors—tumors that typically do not provoke an immune response—and re-engage the immune system that cancer has suppressed. The findings, published in Science Signaling on March 25, are promising for enhancing treatment options for aggressive cancers, such as glioblastoma, which are notoriously challenging to manage.

According to Dr. James Hansen, the senior author of the study and the chief of radiation oncology at Yale’s Gamma Knife Program, the research presents a breakthrough in immunotherapy. “When this antibody penetrates the cytoplasm of cells and attaches to RNA, it prompts a specific recognition receptor to activate, signaling ‘This shouldn’t be here,’ which ignites an immune response,” he explained. Remarkably, the antibody alone has demonstrated a significant prolongation of survival in models of brain tumors, independent of traditional treatment methods like chemotherapy or radiation.

Cold tumors, or immunologically barren environments, characteristically lack T cells, limiting their responsiveness to conventional cancer therapies, including immunotherapies. In contrast, “hot tumors,” which contain immune cells, are generally more responsive, even if temporarily suppressed by the tumor’s presence.

Hansen expressed enthusiasm for this innovative method of mobilizing the immune system to combat brain tumors, saying, “Equally thrilling is the finding that this lupus antibody can deliver genetic material to cells without the use of viruses, which opens up new avenues for gene therapy techniques.”

In laboratory experiments, the researchers confirmed the necessity of functional immune cells for the antibody’s efficacy. The presence of operational immune cells allowed the autoantibody to transport and introduce functional RNA into various tissues, including tumors, brain, and muscle. The study’s authors anticipate that these findings will pave the way for enhanced methods of non-viral gene delivery as well as advancements in immunotherapy.

The study, led by Xiaoyong Chen, featured contributions from other Yale researchers, including 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. Collaborators from UCLA and the Veterans Affairs Greater Los Angeles Healthcare System also played pivotal roles in this groundbreaking investigation.

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