Researchers at MIT have developed a groundbreaking approach to cancer immunotherapy by directly targeting the sugar-based mechanisms tumors use to evade the immune system. The new technique, centered around molecules called “AbLecs” (antibody-lectin chimeras), effectively removes a critical “brake” that cancer cells apply to immune responses, potentially making existing and future immunotherapies far more effective.
How Cancer Evades Immunity
The core problem in cancer treatment is often not the absence of an immune response, but its suppression. Tumors actively use multiple strategies to prevent immune cells – such as T cells, macrophages, and natural killer (NK) cells – from recognizing and destroying them. One of the most promising, yet previously under-addressed, mechanisms involves interactions between sugar molecules (glycans) on cancer cell surfaces and receptors on immune cells.
Specifically, cancer cells often display unusual glycans containing sialic acid. When these bind to Siglec receptors on immune cells, they trigger a dampening pathway that prevents the immune system from attacking. This is analogous to the well-known PD-1/PD-L1 checkpoint blockade, but operates through a different biological route. Existing checkpoint inhibitors target PD-1/PD-L1, and while effective for some, many patients see little to no benefit.
The AbLec Solution: Combining Precision with Power
The MIT team, led by Jessica Stark, solved a key limitation in directly targeting the Siglec-sialic acid interaction: lectins (proteins that bind to sugars) typically lack the necessary strength to accumulate effectively on cancer cells. Their solution? Fuse lectins to antibodies.
The resulting AbLec molecules use the high-precision targeting of antibodies to deliver lectins directly to tumors. Once attached, the lectin blocks sialic acid from binding to Siglec receptors, lifting the immune brake and allowing immune cells to attack. The design is modular, meaning different antibodies can be swapped in to target various cancer types, and different lectins can be used to target other immunosuppressive glycans.
Promising Results in Animal Models
In laboratory tests and animal models, AbLecs demonstrated a clear advantage over traditional antibody therapy. Mice with lung metastases treated with AbLec showed a significant reduction in tumor spread compared to those treated with standard antibodies alone. The researchers successfully tested AbLecs with antibodies targeting HER2, CD20, and EGFR, proving the versatility of the approach.
What This Means for the Future of Cancer Treatment
The development of AbLecs represents a significant step forward in cancer immunotherapy. By tackling a previously under-exploited mechanism of immune evasion, these molecules could unlock new treatment options for patients who do not respond to current therapies. The modular design allows for rapid adaptation to different cancer types, making it a potentially universal platform.
The team has launched Valora Therapeutics to accelerate clinical trials, with the goal of starting human testing within the next two to three years. This breakthrough suggests that overcoming cancer’s immune defenses may soon become more precise, effective, and accessible.
