- Researchers developed antibody lectin hybrids designed to block a sugar based immune brake that tumours use to avoid attack
- The molecules deliver lectins directly to cancer cells, aiming to stop sialic acids from switching off immune cells via Siglec receptors
- Early tests in cells and in mice showed stronger anti tumour effects than the tumour targeting antibody alone
A research collaboration between MIT and Stanford has developed a new approach intended to help the immune system recognise and attack tumours more effectively.
Instead of focusing only on protein checkpoints, the strategy targets sugar patterns on cancer cells that can suppress immune responses.
Checkpoint inhibitors have reshaped cancer treatment by blocking interactions such as PD 1 and PD L 1, which tumours exploit to silence immune cells.
They can produce long lasting benefits for some patients, but many people see little or no effect.
That gap has pushed researchers to look for other immune brakes that tumours can pull.
This work focuses on glycans, the sugar molecules that coat cell surfaces.
Cancer cells often display altered glycan patterns compared with healthy tissue.
Many tumour associated glycans contain sialic acid, a sugar building block that can bind to immune cell receptors called Siglecs.
When Siglecs engage with sialic acids, they can trigger immune dampening pathways that reduce the ability of immune cells to attack.
In principle, blocking this sugar based signalling could lift an immune brake. In practice, one obstacle has been how to do it strongly and selectively.
Lectins, proteins that bind sugars, often have low binding strength on their own, making them difficult to use as standalone therapies.
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The researchers addressed this by building multifunctional molecules called AbLecs. Each AbLec pairs a tumour targeting antibody with a lectin that binds sialic acid.
The antibody acts as a delivery vehicle that concentrates the lectin at the cancer cell surface.
Once there, the lectin can occupy sialic acids, blocking them from engaging Siglec receptors on immune cells. The intended result is less immune suppression and more immune attack, including activity from macrophages and natural killer cells.
For an initial demonstration, the team used trastuzumab, an antibody that targets HER2 and is already used in several cancers.
They replaced one arm of the antibody with a lectin based on Siglec 7 or Siglec 9.
In lab experiments, these hybrids altered immune cell behaviour in ways that increased cancer cell killing.
They then tested the approach in mice engineered to express human Siglec receptors and human antibody receptors.
In a model where injected cancer cells formed lung metastases, treatment with the AbLec led to fewer lung metastases than treatment with trastuzumab alone.
A key strength of the concept is modularity. The antibody component can be swapped to target different tumour markers and the lectin component can be swapped to target other immunosuppressive glycans.
The same framework could also be combined with antibodies aimed at established checkpoint pathways.
The results are early stage and far from proving clinical benefit in humans, but they open up a new direction for immunotherapy.
Instead of only blocking protein checkpoints, the approach aims to block sugar driven immune suppression that may operate across multiple tumour types.
