MIT scientists develop method to remove cancer cells' protective sugar coating

Immunotherapy has revolutionized cancer treatment by teaching the immune system to recognize tumors, yet many patients still fail to respond to the most successful drugs, known as checkpoint inhibitors. These treatments block proteins like PD-1 and PD-L1, which act like brakes on immune cells. However, scientists have recently discovered another lesser-known “checkpoint”: sugar-coated structures called glycans. Tumor cells decorate themselves with unusual glycans rich in a sugar called sialic acid, which binds to receptors named Siglecs on immune cells, silencing their attack.

Led by Dr. Jessica Stark at MIT’s Koch Institute and Nobel laureate collaborator Dr. Carolyn Bertozzi at Stanford, the researchers designed AbLecs to block this sugar-based immune brake. Each AbLec links a lectin protein, which can bind sialic acids, to a tumor-targeting antibody. The antibody delivers the lectin directly to cancer cells, where it locks onto the glycans and prevents them from engaging Siglec receptors, freeing macrophages and natural killer (NK) cells to attack.

In laboratory experiments, AbLecs revived immune activity against tumor cells that had previously gone undetected. In mouse models engineered with human immune receptors, a HER2-targeted AbLec significantly reduced lung metastases compared to its parent antibody, trastuzumab (Herceptin), used for breast and stomach cancers. The platform proved adaptable too—by swapping the antibody component (to drugs like rituximab or cetuximab) or altering the lectin type, the molecule can be “re wired” for multiple cancer types.

The discovery opens an exciting frontier in immunotherapy—one that targets cancer’s hidden sugar shield instead of protein switches alone. If further clinical testing confirms these results, AbLecs could become a new class of smarter, more adaptable treatments that help extend immunotherapy’s success to far more patients.

REFERENCE: Jessica C. Stark, Melissa A. Gray, Itziar Ibarlucea-Benitez, Marta Lustig, Annalise Bond, Brian Cho, Ishika Govil, Tran Luu, Megan J. Priestley, Tim S. Veth, Wesley J. Errington, Bence Bruncsics, Mikaela K. Ribi, Leo A. Williams, Casim A. Sarkar, Simon Wisnovsky, Nicholas M. Riley, Meghan A. Morrissey, Thomas Valerius, Jeffrey V. Ravetch, Carolyn R. Bertozzi. Antibody-lectin chimeras for glyco-immune checkpoint blockade. Nature Biotechnology, 2025; DOI: 10.1038/s41587-025-02884-6