Nanobodies prove superior to antibodies for cancer vaccine targeting


Nov 04, 2024 (Nanowerk Spotlight) The human immune system can be a powerful weapon against cancer, but only if it can be taught to recognize tumor cells as threats. Medical researchers have developed vaccines that train immune cells to fight cancer, but delivering these vaccines to the right cells remains a critical challenge. The vaccines must reach specialized immune cells called dendritic cells, which act as teachers for the immune system by showing other cells what to attack. Current cancer vaccines use antibodies as targeting systems to find these dendritic cells. Antibodies are Y-shaped proteins that can lock onto specific structures on cell surfaces, like a key fitting into a lock. While effective at targeting, antibodies present several problems. They require complex chemical modifications before they can be attached to vaccine-carrying particles, a process that takes several days and significantly increases production costs. Antibodies also contain parts that can trigger unwanted immune responses, potentially reducing their effectiveness. Scientists have tried various methods to improve this targeting system. Many approaches worked well in laboratory dishes but failed in living organisms. The human body’s complex environment often caused these targeting systems to miss their intended cells entirely, rendering the vaccines ineffective. Now, researchers at the Max Planck Institute for Polymer Research and the University Medical Center of Johannes Gutenberg University Mainz have developed a simpler solution using nanobodies. These nanobodies, derived from camels and their relatives, are smaller, simpler versions of antibodies that maintain targeting precision while avoiding many complications. The findings have been published in Advanced Materials (“Nanobodies Outperform Antibodies – Rapid Functionalization with Equal In Vivo Targeting Properties”). The team created vaccine-carrying particles equipped with nanobodies that seek out dendritic cells. Unlike antibodies, these nanobodies come with a built-in attachment point – a specific amino acid that allows them to be connected to the vaccine particles in hours rather than days. This attachment uses a straightforward chemical reaction that maintains the nanobodies’ targeting ability. Replacement of the previously reported antibody-based system with a nanobody-based nanocarrier system leads to a significantly reduced functionalization time while maintaining targeting properties Concept overview. Replacement of the previously reported antibody-based system with a nanobody-based nanocarrier system leads to a significantly reduced functionalization time while maintaining targeting properties. (Image: Reprinted from DOI:10.1002/adma.202412563, CC BY) To verify their system’s effectiveness, the researchers conducted detailed comparisons with traditional antibody methods. They used advanced microscopy and molecular tracking techniques to count exactly how many nanobodies attached to each particle’s surface. This precise measurement matters for future medical approval processes. The team tested their system in three increasingly complex scenarios. First, they used laboratory-grown dendritic cells, where both antibody and nanobody systems performed well. Next, they tested cells taken directly from mouse bone marrow, which better represent natural conditions. Finally, they injected the particles into living mice to track where they accumulated. In living mice, the nanobody system matched the targeting precision of antibodies. The vaccine particles found their way specifically to dendritic cells while avoiding other cell types. This selective delivery ensures that vaccine components reach only the cells capable of initiating an anti-cancer immune response. The researchers also investigated how their particles interact with blood proteins. When any foreign material enters the bloodstream, proteins quickly coat its surface, potentially changing how cells respond to it. Both antibody and nanobody systems attracted similar proteins, suggesting that the nanobody system’s efficiency comes from its targeting ability rather than from different blood interactions. This new approach solves several practical problems in cancer vaccine development. The simpler production process could accelerate vaccine development by making it easier to test different combinations of components. The precise control and measurement of nanobody attachment provides crucial data for regulatory approval processes. The system’s combination of precision and practicality represents a significant advance in cancer immunotherapy. By maintaining targeting accuracy while dramatically simplifying production, this nanobody approach could speed the development of new cancer vaccines without compromising their effectiveness. The researchers’ work establishes a foundation for creating cancer vaccines that could move from laboratory to patient more quickly and at lower cost.


Michael Berger
By
– Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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