VUB research marks a step forward in using Nanobodies® to destroy cancer cells
Bioengineer Ema Romão (VUB's Brussels Centre for Immunology) developed and tested so-called Nanobodies®—antibodies derived from camelids—as part of her PhD research at the Vrije Universiteit Brussel (VUB). These Nanobodies® specifically target key molecules involved in cancer research, including the CD47-SIRPα immune checkpoint axis. The CD47-SIRPα axis acts as a signalling mechanism that cells use to indicate that they belong to the body and should therefore not be attacked by the immune system.
Antibodies have long been used in diagnostics and therapies for a wide range of diseases, including cancer. Conventional monoclonal antibodies—laboratory-engineered proteins designed to recognise and bind to a single specific target (antigen), such as a protein on a cancer cell or a virus—have nevertheless shown certain limitations. Due to their relatively large size, they struggle to penetrate solid tumours and complex tissues. Their production is also costly and technically demanding.
According to Romão, Nanobodies® offer a promising alternative. “They are approximately ten times smaller than conventional antibodies”, she explains. “As a result, they can penetrate much deeper into tumours and are particularly well suited to reaching highly specific targets.” In addition, they are more stable, easier to produce, and more readily adapted for medical applications.
In her doctoral research, Romão investigated how Nanobodies® can be used to counter mechanisms that tumours employ to evade the immune system. One part of the research focused on the CD47-SIRPα axis. CD47 is a protein found on the surface of cells, while SIRPα is a receptor present on immune cells such as macrophages, the body's cellular “clean-up crew”. When CD47 binds to SIRPα, the macrophage receives a signal to leave that particular cell untouched.
Many cancer cells exploit this mechanism by producing excessive amounts of CD47. In doing so, they effectively hide from the immune system and avoid being destroyed. Researchers are therefore seeking therapies capable of blocking this interaction, enabling immune cells to recognise and eliminate tumour cells.
Romão developed Nanobodies® that specifically bind to either CD47 or SIRPα and investigated how effectively they could block this interaction. “We found that certain Nanobodies® are capable of reactivating phagocytosis, the process by which immune cells engulf and break down unwanted invaders or cellular debris”, says Romão. “In other words, they help the immune system recognise and remove tumour cells once again.”
Several of these Nanobodies® were subsequently radiolabelled to study their behaviour in living mouse models. Radiolabelling makes it possible to track the Nanobodies® after administration, revealing which organs and tissues they reach and how long they remain there. Using this approach, the researchers demonstrated that the molecules distribute throughout the body and successfully reach their intended targets.
“Our results show that Nanobodies® are not only powerful research tools, but also hold considerable potential as the basis for new diagnostic and therapeutic applications in oncology”, says Romão. “The field is still relatively young, but the possibilities are enormous.”
About the researcher
Ema Romão obtained a Master's degree in Biomolecular Sciences from the VUB in 2013. She subsequently began a PhD in Bioengineering Sciences under the supervision of Professor Serge Muyldermans, a pioneer in Nanobody research. Following his retirement, the supervisory role was taken over by Prof. Dr Ir. Jo Van Ginderachter. Her work was supported first by a fellowship from the Research Foundation – Flanders (FWO) and later by a grant from the King Baudouin Foundation. During her PhD, she published three first-author scientific papers and contributed to seventeen additional international publications. She also presented her work at international conferences and supervised seven Master's students.
PhD title: Development of Nanobodies with Therapeutic and Diagnostic Potential in Cancer
More information
Ema Romão: Ema.Estevens.Romao@vub.be
Supervisor: Prof. Dr Ir. Jo Van Ginderachter: Jo.Van.Ginderachter@vub.be
Frans Steenhoudt
