Cancer has a talent for hiding in plain sight, cloaking itself in sugary molecules that convince the immune system to stand down. Researchers at MIT and Stanford have now engineered a way to rip away that protective coating, exposing tumors to immune attack in a way that could be adapted across many cancer types. Their work reframes the sugar layer on tumor cells not as a passive decoration but as an active shield that can be targeted, customized and, crucially, removed.
By fusing sugar-binding proteins to tumor-homing antibodies, the teams have built modular molecules that latch onto cancer cells and block the glycans that help them evade detection. The approach, tested in cells and in mice, points toward a new class of immunotherapies that do not just press harder on the immune system’s accelerator, but also release the brakes that tumors have installed at the molecular level.
How cancer’s sugar shield keeps immune cells at bay
To understand why this work matters, I need to start with the shield itself. Cancer cells are coated in complex chains of sugars, or glycans, that are stitched onto proteins and lipids at their surface. These glycans are not random decoration. They are carefully arranged patterns that interact with immune receptors and help determine whether a cell is treated as friend or foe. In tumors, those patterns are often altered in ways that dampen immune responses, a strategy that fits squarely into what researchers describe as “How Cancer Uses Immune Brakes.”
Immune cells read these sugar patterns through receptors that recognize specific glycan motifs and then send signals that either activate or restrain an attack. Tumors exploit this system by displaying glycans that engage inhibitory pathways, effectively telling T cells and other defenders to back off. The result is a biochemical disguise, a sugar shield that lets malignant cells grow even when the immune system is otherwise primed to fight. The new work from MIT and Stanford targets that shield directly, treating the altered glycans as a vulnerability rather than an immutable feature of cancer biology.
From immune brakes to plug-and-play targeting
Traditional immunotherapies have focused on either boosting immune activity or blocking protein-based checkpoints such as PD-1 and CTLA-4. The MIT teams took a different angle, asking how to interfere with the glycan signals that contribute to those immune brakes. Their answer is a modular construct that combines a tumor-targeting antibody with a sugar-binding component, designed so that the antibody guides the molecule to cancer cells while the lectin portion interferes with the glycans that help those cells hide. In effect, they are building a plug-and-play system that can be retuned to different tumors by swapping out the antibody component.
In laboratory work that fed into the current advance, the scientists described a “plug and play” design tested in cells and in mice, where they created an AbLec by attaching a lectin to an antibody fragment and then showed that the targeting could be redirected simply by changing the antibody target. That modularity, detailed in their description of how they created the AbLec, is central to the promise of this approach. It means the same basic scaffold could, in principle, be adapted to breast tumors, lung tumors or blood cancers simply by choosing a different antibody that recognizes a marker on those cells.
Researchers at MIT and Stanford University join forces
The work is the product of a collaboration that brings together expertise in immunology, protein engineering and cancer biology. Researchers at MIT and Stanford University set out to design a new way to stimulate the immune system to attack tumor cells by combining a lectin with a tumor-targeting antibody. Their goal was not just to add another checkpoint inhibitor to the arsenal, but to create a platform that could be tuned to many tumor types without rebuilding the entire therapy from scratch each time.
In their description of this new immunotherapy approach, the teams explain how they linked sugar-binding proteins to antibodies that home in on cancer cells, creating a hybrid molecule that both finds tumors and interferes with their glycan-based defenses. By showing that these constructs can enhance immune activity against tumor cells in preclinical models, the Researchers at MIT and Stanford University have positioned this strategy as a candidate for broad, rather than niche, application. That breadth is particularly important in immunotherapy, where many existing drugs work only for a subset of patients with specific mutations or immune profiles.
Scientists at MIT and Stanford strip away the sugar disguise
Earlier this month, Scientists at MIT and Stanford reported that they had unveiled a promising new way to help the immune system recognize and attack cancer by directly targeting the sugar coating on tumor cells. Their engineered molecules, which they call AbLecs, are designed to bind to glycans that are abundant on cancer cells and then block those sugars from engaging immune-suppressive receptors. By doing so, they effectively strip away the sugar disguise that has been shielding the tumor from immune surveillance.
In preclinical experiments, the teams showed that these AbLecs could dramatically boost immune activity against cancer cells, both in cell cultures and in mouse models. The constructs did not simply sit on the tumor surface. They altered the way immune cells perceived those tumors, leading to stronger activation and more robust killing. The report that Scientists at MIT and Stanford had achieved this effect underscores how central the glycan layer is to immune evasion. It also suggests that targeting sugars could complement, rather than replace, existing checkpoint inhibitors that focus on protein-based signals.
Engineering AbLecs to block glycans and unmask tumors
The core innovation in this work is the AbLec itself, a fusion of an antibody fragment and a lectin that can recognize and bind specific glycans. By blocking those glycans with molecules called lectins, the researchers showed they could dramatically boost the immune response against tumor cells. The lectin portion of the AbLec latches onto the sugar structures that are overrepresented on cancer cells, while the antibody fragment ensures that the construct is delivered precisely to the tumor, minimizing off-target effects on healthy tissue.
In detailed accounts of their experiments, the teams describe how they combined a lectin with a tumor-targeting antibody to create a molecule that both recognizes and disrupts the glycan shield. When these AbLecs were applied to tumor cells, immune cells that had previously ignored those targets began to respond more vigorously, producing signals associated with activation and cytotoxicity. The finding that they could, by blocking those glycans with molecules called lectins, overcome cancer’s immune evasion tactics gives the AbLec design a clear mechanistic rationale. It is not just binding to tumors, it is actively dismantling one of their key defenses.
Lectins, dendritic cells and the broader sugar-binding toolkit
The AbLec strategy does not emerge in a vacuum. It builds on a growing body of work that treats sugar-binding proteins as powerful tools for immunotherapy. Lectins, in particular, have attracted attention because they naturally recognize specific glycan motifs and can be engineered or repurposed to deliver therapeutic payloads. In the context of cancer, lectins can be used to either block suppressive glycans or to ferry drugs and immune stimulants directly to cells that display those sugar patterns.
Recent studies on mannose mimicking glycopolymer nanoparticles highlight how sugar-binding proteins like lectins in cells interact with macromolecular chains during cell recognition and adhesion, and how those interactions can be harnessed to activate dendritic cells. By showing that these nanoparticles can induce dendritic cell activation, the work positions lectin-based systems as an apt choice for immunotherapeutic delivery, not just for targeting tumors but also for priming the immune system upstream. The report that the sugar-binding proteins like lectins in cells make an apt choice for immunotherapeutic delivery reinforces the logic of using lectin domains in AbLecs. It suggests that the same molecular recognition that guides dendritic cell activation can be repurposed to unmask tumors and coordinate a more effective immune response.
Redirecting the immune system through altered glycans
One of the most intriguing aspects of this research is the idea that altered glycans on tumor cells can be treated as targets in their own right, not just as background features. Here, the scientists present an approach to redirect the immune system into fighting cancer by focusing on those altered glycans and designing molecules that bind them with high affinity. Instead of relying solely on protein antigens that may vary from tumor to tumor, they are exploiting common glycan signatures that appear across different cancers, potentially widening the reach of a single therapeutic design.
To do this, they link a lectin to an antibody fragment, creating a construct that can both recognize the glycan pattern and engage immune effector mechanisms through the antibody domain. This dual recognition, of sugars and of immune machinery, is what allows the therapy to both find and flag tumor cells for destruction. In technical descriptions of the strategy, the researchers explain that Here they present an approach to redirect the immune system by targeting altered glycans at the surface of cancer cells using a lectin linked to an antibody fragment. That concept dovetails neatly with the AbLec design and underscores a broader shift in immuno-oncology, where sugars are moving from the periphery of attention to the center of therapeutic strategy.
What comes next for sugar-focused immunotherapy
For all its promise, the sugar shield strategy is still in its early stages, and I see several hurdles that will shape what comes next. Safety is one. Glycans are not unique to tumors, and many healthy cells rely on similar sugar patterns for normal function. The challenge will be to identify glycan motifs that are sufficiently enriched or structurally distinct on cancer cells so that AbLecs and related constructs do not trigger widespread collateral damage. The modularity of the plug-and-play design helps here, because it allows researchers to fine-tune both the lectin specificity and the antibody targeting as they learn more about which combinations offer the best balance of potency and selectivity.
Another question is how these sugar-focused therapies will integrate with existing treatments. It is unlikely that AbLecs will replace checkpoint inhibitors, CAR-T cells or conventional chemotherapy in the near term. Instead, they may find their greatest value as part of combination regimens, where stripping away the glycan shield makes tumors more vulnerable to other immune attacks or to targeted drugs. The fact that the underlying concepts have already been tested in cells and in mice, and that they build on a foundation of work with lectins, dendritic cell activation and high-affinity anti-glycan antibodies, suggests that the field is moving from theoretical possibility to practical experimentation. If the early promise holds up in human trials, the sugar layer that once helped cancer hide could become one of its most exploitable weaknesses.
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