Nanobody: the hope for future medicine

Using antibodies from alpacas, a research team from the University of Kentucky has developed a tool that could pave the way for new cancer therapies.

Previous studies have established a connection between a protein called PRL-3 and the growth of various cancers, including colon, breast, lung, skin, and blood cancers. However, due to a lack of effective tools for studying this protein, there is limited understanding of how it functions.

Led by Dr. Jessica Blackburn from the UK Markey Cancer Center, the research team has successfully created nanobodies - distinct alpaca antibodies - that specifically target PRL-3. This breakthrough discovery brings scientists one step closer to developing a drug that can inhibit the expression of PRL-3 and impede cancer growth.

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Dr. Blackburn explains that these nanobodies are valuable tools for better understanding how PRL-3 contributes to the progression of cancer. By pinpointing PRL-3 within cancer cells, the nanobodies can offer insights into its interactions with other proteins and molecules, ultimately enhancing our comprehension of its role in cancer. Additionally, they have the potential to be used therapeutically by binding to PRL-3 and inhibiting its activity.

The effectiveness of the PRL-3 nanobodies was demonstrated in laboratory tests conducted in collaboration with UK's Protein Core, and the results were published in the journal PLOS ONE. The nanobodies were able to identify PRL-3 within cancer cells and bind to its active site, potentially interfering with its ability to promote cancer growth. Furthermore, they reduced the interaction between PRL-3 and another protein called CNNM3, which is known to contribute to cancer growth in animal models.

Alpacas are rare among animals in their ability to produce nanobodies, also known as single domain antibodies or heavy chain only antibodies. Nanobodies are significantly smaller than traditional antibodies, allowing them to enter cells in ways that regular antibodies cannot. This unique characteristic makes them a promising tool for understanding diseases and developing drugs.

Although alpaca nanobodies are relatively uncommon, the UK Protein Core has been at the forefront of producing them for biomedical research. Over the past six years, they have generated more than 100 nanobodies targeting proteins associated with various human diseases, including cancer, diabetes, neurological disorders, and viruses like COVID-19.

The process involves immunizing alpacas with the protein of interest and collecting blood samples after six weeks. From these samples, researchers identify, isolate, test, and reproduce the nanobodies that specifically target the protein.

This research endeavor requires collaboration across different disciplines, specialized equipment, and, of course, alpacas. The UK Protein Core has established a partnership with a local alpaca farm, where the animals are primarily housed. They visit UK's North Farm for immunization and blood collection.