When it comes to Cancer Immunotherapy, you may have heard of CAR-T and bispecific antibodies, but these therapies have a fatal flaw—they require finding protein targets unique to cancer cells. However, most cancers don't have exclusive proteins, or the targets are also present on normal cells, easily leading to collateral damage and serious side effects.
On November 26, 2025, a groundbreaking study published in Cell by Michael Demetriou from the University of California completely broke this deadlock. Scientists developed a new type of immunotherapy called glycan-dependent T cell recruiter (GlyTR), which doesn't target proteins, but instead targets sugar molecules on the surface of cancer cells.
Even more remarkably, it acts like Velcro, only attaching to cancer cells with a high density of sugar molecules, ignoring normal cells with fewer sugar molecules. This allows it to efficiently kill multiple types of cancer without worrying about mistakenly killing healthy cells.
Fig. 1 Safe immunosuppression-resistant pan-cancer immunotherapeutics by velcro-like density-dependent targeting of tumor-associated carbohydrate antigens. (Zhou, et al. 2025)
You may not know that cancer cells are covered with a large number of abnormal sugar molecules, a key feature that distinguishes them from normal cells:
Unfortunately, traditional antibody therapy has difficulty grasping these sugar molecules—the sugar molecules have flexible structures, and the antibody affinity is low, like trying to pick up soap with tweezers; it simply can't be held. The emergence of GlyTR solves this problem.
The secret of GlyTR lies in combining two powerful tools to form a bispecific protein:
Simply put, GlyTR is like a "precision-guided missile," first using "Velcro" to find cancer cells, and then summoning T cells to destroy them, without touching normal cells throughout the process.
The research team developed two GlyTRs, each targeting different sugar molecules, covering the vast majority of cancers:
GlyTR1: Specifically kills cancers with high levels of β1,6 branched glycans and can also overcome immunosuppression.Experiments show that in humanized mouse models, GlyTR1 significantly reduced or even eliminated tumors in pancreatic cancer, triple-negative breast cancer, and ovarian cancer. Even when the tumor is full of exhausted T cells (severe immunosuppression), GlyTR1 can reactivate them and kill cancer cells.
GlyTR2: One drug kills multiple cancers, covering 90% of epithelial cancers.In tests, GlyTR2 was effective against triple-negative breast cancer, leukemia, and ovarian cancer, and caused no damage to normal cells (such as red blood cells and kidney cells) because these cells do not have a high enough density of these sugar molecules for GlyTR2 to bind to.
Traditional CAR-T and bispecific antibodies require finding specific protein targets for each type of cancer, such as CD19 only targeting B-cell lymphoma, and HER2 only targeting some breast cancers. GlyTR, however, targets sugar molecules, which are a universal marker for almost all cancers. One GlyTR can treat multiple solid tumors and hematological cancers, eliminating the need to develop a separate drug for each type of cancer.
Many previous immunotherapies caused serious side effects because their targets were also present on normal cells (e.g., cytokine storm from CAR-T, neurotoxicity from bispecific antibodies). GlyTR, however, relies on density recognition; it only binds when the density of sugar molecules reaches the standard of cancer cells. Even if normal cells have the same sugar molecules, they escape harm due to their lower density.
Experiments have confirmed that injecting therapeutic doses of GlyTR1 and GlyTR2 into humanized mice resulted in no change in mouse weight, and liver and kidney function and blood counts remained normal. Even organs with high sugar molecule content, such as the kidneys and intestines, showed no damage, meaning it only kills cancer cells without harming healthy cells.
Currently, GlyTR1 has entered the GMP production stage and is planned for Phase I clinical trials targeting refractory solid tumors. Its advantages may be even more pronounced in advanced cancer patients, because the further cancer cells metastasize, the higher the density of sugar molecules on their surface, and the stronger the killing effect of GlyTR.
In the future, this therapy has even more possibilities:
The bottleneck in cancer immunotherapy has always been the inability to find precise targets and the tendency to harm normal cells. The emergence of GlyTR, using sugar molecules—a previously overlooked target—combined with a Velcro-like density recognition design, perfectly solves these two problems. For patients, this means that in the future they may no longer have to wait for specific targeted drugs; one GlyTR drug could treat multiple Cancers, and with fewer side effects. Perhaps it won't be long before pan-cancer immunotherapy moves from the laboratory to clinical practice, bringing hope to more cancer patients.
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