Yale scientists have discovered a lupus-related antibody that can trigger immune responses in hard-to-treat cancers, offering new hope for therapies against glioblastoma and other aggressive tumors.
In a groundbreaking study, Yale University scientists have identified a promising new way to activate immune responses against certain difficult-to-treat tumors. The research, published in Science Signaling, reveals that a lupus-related antibody can infiltrate “cold” tumors, which typically evade the immune system, and activate an immune response.
“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,” senior author James Hansen, the radiology oncology chief of Yale’s Gamma Knife Program and a member of the Yale Cancer Center, said in a news release.
By leveraging this antibody, researchers have been able to prolong survival in brain tumor models without the need for traditional treatments like radiation or chemotherapy.
Cold tumors, often referred to as immune deserts, are challenging to treat because they lack immune cells such as T cells. This makes them unresponsive to most cancer treatments, including immunotherapies that rely on the presence of these cells.
Conversely, “hot tumors” do respond to treatments since they have immune cells, even if those cells are temporarily suppressed by the cancer.
“We’re excited about this new way to engage the immune system to treat brain tumors,” added Hansen. “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 study confirms that the antibody is ineffective in tissue that lacks functional immune cells. However, when immune cells function correctly, the antibody can deliver functional RNA into tumor, brain and muscle tissue.
This finding could revolutionize non-viral gene delivery methods, which utilize physical forces rather than viruses to introduce genetic material into cells, and provide new avenues for immunotherapy treatments.
Joining Hansen in this groundbreaking research was first author Xiaoyong Chen of Yale. The collaborative effort included contributions from 12 other Yale scientists, as well as researchers from UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.
This breakthrough has the potential to significantly enhance the efficacy of current cancer treatments, transforming how aggressive cancers like glioblastoma are treated and providing a beacon of hope for patients worldwide.
Source: Yale School of Medicine