Researchers from the Massachusetts Institute of Technology (MIT) and Stanford University have unveiled a promising new immunotherapy approach that helps the immune system recognize and attack cancer cells more effectively by dismantling a previously hidden immune “off switch” used by tumors
Cancer cells often evade immune detection by coating themselves with specialized sugar molecules known as glycans. These glycans interact with immune cell receptors called Siglecs, suppressing immune activity and preventing immune cells from attacking tumors. While current checkpoint inhibitors target protein-based pathways such as PD-1/PD-L1, many patients show limited or no response, highlighting the need for alternative immune targets.
The MIT–Stanford team developed a new class of hybrid molecules called antibody–lectin chimeras (AbLecs) to overcome this challenge. These engineered molecules combine the tumor-targeting precision of antibodies with lectins, proteins that bind to glycans, allowing them to block glycan-mediated immune suppression directly at the tumor surface.
By attaching lectins to antibodies that already home in on cancer cells, the researchers ensured that lectins accumulate effectively where they are needed most. Once bound, AbLecs prevent tumor glycans from interacting with Siglec receptors on immune cells, effectively releasing the immune “brake.” This enables immune cells such as macrophages and natural killer cells to recognize and destroy cancer cells more efficiently.
In laboratory experiments, AbLecs significantly enhanced immune cell activity against cultured cancer cells. The approach was also tested in mice engineered to express human immune receptors. In these models, treatment with AbLecs resulted in fewer lung metastases compared with treatment using standard antibody therapies alone, indicating superior anti-tumor efficacy.
Importantly, the AbLec system was designed as a modular, plug-and-play platform. Researchers demonstrated that both components of the molecule can be swapped: different antibodies can be used to target various cancer types, while different lectins can be employed to block multiple glycan-based immune checkpoints. This flexibility increases the potential applicability of the approach across a wide range of tumors.
The study was led by Jessica C. Stark of MIT’s Koch Institute for Integrative Cancer Research, with Carolyn R. Bertozzi of Stanford University serving as senior author. The findings were published in Nature Biotechnology, highlighting the growing recognition of glycan-based immune regulation as a critical frontier in cancer therapy
To accelerate translation into clinical applications, the research team has launched a startup company, Valora Therapeutics, with plans to initiate early-stage clinical trials within the next two to three years. If successful, AbLecs could represent a new generation of immunotherapies capable of overcoming resistance to existing checkpoint inhibitors and improving outcomes for cancer patients worldwide.