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MIT and stanford Researchers Develop Novel Cancer Immunotherapy
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A research team from MIT and Stanford University has developed a new technique designed to push the immune system to go after tumor cells. The strategy is aimed at helping cancer immunotherapy succeed in far more patients than it does today.
At the center of the work is a way to undo a built-in “brake” that tumors can trigger to keep immune cells from attacking.that brake is tied to sugars called glycans, which sit on the surface of cancer cells.
The scientists found that blocking thes glycans with proteins known as lectins can greatly strengthen immune activity against cancer cells.To do this in a targeted way, they built multifunctional molecules called AbLecs that pair a lectin with an antibody that homes in on tumors.
“We created a new kind of protein therapeutic that can block glycan-based immune checkpoints and boost anti-cancer immune responses,” says Jessica Stark,the Underwood-Prescott Career Growth Professor in the departments of Biological Engineering and Chemical Engineering.”Because glycans are known to restrain the immune response to cancer in multiple tumor types, we suspect our molecules could offer new and potentially more effective treatment options for many cancer patients.”
Stark, who is also a member of MIT’s Koch Institute for Integrative Cancer Research, led the study as the paper’s lead author. Carolyn Bertozzi, a Stanford professor of chemistry and director of the Sarafan ChEM Institute, served as the senior author. The findings were published in Nature Biotechnology.
How Cancer Uses Immune Brakes
One of the biggest goals in cancer treatment is teaching the immune system to spot tumor cells and eliminate them. A major group of immunotherapy drugs called checkpoint inhibitors works by interrupting the interaction between two proteins, PD-1 and PD-L1. by blocking that connection, these medicines remove a brake that tumors use to keep immune cells such as T cells from killing cancer cells.
Checkpoint inhibitors that target the PD-1/PD-L1 pathway are already approved for several cancers. For some people, they can produce long-lasting remission. For many others, however, they don’t work at all. This is because tumors can employ other mechanisms to evade the immune system.
The research team focused on glycans, sugar molecules that coat the surface of cells. Cancer cells often display unusual glycan patterns that suppress immune responses. these glycans bind to receptors on immune cells, effectively telling them to stand down.
AbLecs: A Targeted Approach
To overcome this glycan-mediated immune suppression, the researchers developed AbLecs. These molecules combine the specificity of antibodies – which target cancer cells – with the glycan-blocking ability of lectins. The antibody guides the AbLec directly to the tumor, where the lectin component binds to the glycans and prevents them from inhibiting immune cell activity.
In preclinical studies, AbLecs demonstrated a notable ability to enhance the activity of T cells against cancer cells. They also showed promise in combination with existing checkpoint inhibitors,suggesting a potential strategy to overcome resistance to those therapies.
Future Directions
The researchers are now working to optimize AbLecs and test them in more complex models of cancer. They are also exploring whether these molecules could be used to treat other diseases where immune suppression plays a role.
Key Takeaways
- Researchers have identified glycans as a key mechanism tumors use to evade the immune system.
- AbLecs, a novel molecule combining antibodies and lectins, effectively block these glycans and boost anti-cancer immune responses.
- Preclinical studies show AbLecs enhance T cell activity and may overcome resistance to existing immunotherapies.
- This research offers a promising new avenue for developing more effective cancer treatments.
FAQ
Q: What are glycans and why are they significant in cancer?
A: Glycans are sugar molecules found on the surface of cells. Cancer cells often display altered glycan patterns that suppress the immune system, helping them avoid detection and destruction.
Q: What are ablecs