Our immune system protects us by detecting threats like viruses, bacteria, and cancer cells. Dendritic cells are one of the most important types of immune cells because they decide how the rest of the immune system should respond. However, scientists still do not fully understand how to "guide" dendritic cells to create the strongest and safest immune responses.
In the LectiNet project, we created a library of over 50 small, synthetic molecules that mimic the way germs naturally interact with dendritic cells. We tested these molecules in human immune cells in the lab and discovered that small changes in their structure could lead to very different immune reactions. From testing our library on dendritic cells we could draw some major conclusions:
Targeting Multiple Receptors at Once- We found that our synthetic molecules could successfully attach to and activate rare receptors on dendritic cells, even when other more common receptors were present. This shows that it is possible to design vaccines or treatments that precisely target less abundant parts of the immune system to fine-tune the response.
Each Molecule Creates a Unique Immune Response- Each different combination of sugars and immune activators on our synthetic molecules caused dendritic cells to behave in slightly different ways. Some molecules made the cells show stronger "activation signals," which are important for telling the rest of the immune system to respond.
Soluble Molecules Are Less Powerful Adjuvants- While our soluble molecules were good at activating dendritic cells, they did not strongly trigger the release of immune system messenger molecules called cytokines. This suggests that, in their current form, these molecules may need further modification (for example, by being made into particles) before being used as vaccine adjuvants in living organisms.
To overcome the minor immonogenic power of the soluble polimers, we also created a particulate, stiffer vaccine candidate that combined two different signals to better activate the immune system. We tested this vaccine in mice with an aggressive form of melanoma (a type of skin cancer). The vaccine was able to reach the right areas of the body, activate important immune cells, and trigger an antibody response.
Through this work, LectiNet has taken important steps toward designing better vaccines and immune therapies that could, in the future, help treat diseases like cancer and infections more effectively and safely.
