Radiotherapy and “Minibindersâ€
The Washington Research Foundation (WRF) has awarded a $387,050 grant to Dr. Derrick Hicks and his team at the University of Washington’s Institute for Protein Design (IPD) to further develop a groundbreaking radiotherapy technology. This new funding builds upon previous support totaling $350,000 provided by WRF in 2022 and 2023.
Radiotherapies, which use radiation to target and kill cancer cells, are vital tools in cancer treatment. However, traditional radiotherapies can cause significant damage to healthy cells surrounding tumors, which limits their effectiveness and increases the risk of side effects. Radiolabeled antibodies—antibodies that are attached to a radioactive atom—have made strides in improving the precision of radiation therapy. By binding specifically to cancer cells, these antibodies help minimize radiation exposure to healthy tissues. Despite their promise, antibodies are large molecules, making it difficult for them to penetrate the tumor microenvironment and reach their targets effectively. Additionally, their prolonged circulation in the body can result in unwanted exposure to non-target tissues.
Dr. Hicks and his collaborators are working to overcome these challenges by using “minibinders,” small protein molecules engineered for highly specific targeting. Unlike traditional antibodies, minibinders are compact and designed to bind tightly to specific tumor markers, allowing them to more efficiently navigate the tumor microenvironment. Historically, developing these minibinders required substantial trial-and-error experiments, but recent advances in machine learning at the IPD have accelerated the process, enabling faster identification of optimal protein candidates.
The team plans to attach radioactive atoms to minibinders in order to create new therapies that can target cancer cells more precisely. These minibinders are expected to be small enough to penetrate tumors and sufficiently specific to bind only to cancer cells, reducing the potential for damage to healthy tissues. Importantly, minibinders can be designed to be excreted from the body over time, minimizing toxic effects.
The research collaboration includes notable scientists such as Dr. Gonçalo Bernardes of the University of Cambridge and the Institute of Molecular Medicine in Lisbon, as well as Dr. Bruno Oliveira from the Center for Nuclear Sciences and Technologies in Lisbon, who will help with the radiation-related aspects of the study.
The WRF funding will support the optimization of these minibinder-radioactive atom conjugates, with a focus on targeting proteins that are overexpressed in tumors and crucial for their survival and spread. These compounds will also be tested for their potential to be used in diagnostic imaging through positron emission tomography (PET). PET imaging allows for detailed 3D scans of the body using radiotracers, helping doctors visualize tumors. The researchers aim to determine whether their minibinders can make tumors visible using PET, which would allow the technology to serve as both a diagnostic and a therapeutic tool.
Dr. Hicks emphasized that this funding will help the team move closer to developing effective treatments for patients with aggressive cancers and high unmet medical needs. The team’s goal is to create therapies that selectively target and destroy cancer cells while sparing healthy tissue.
Dr. Meher Antia, WRF’s director of grant programs, expressed confidence in the progress made so far and the potential of this technology. She stated that WRF is excited to continue supporting this promising work. Dr. Hicks anticipates that the project will be completed within a year and is considering forming a spin-off company from the IPD to help commercialize the technology and move it toward clinical trials.
Commentary by YourDailyFit Columnist Alice Winters:
The research being spearheaded by Dr. Derrick Hicks and his team at the University of Washington represents a noteworthy evolution in the field of radiotherapy, combining precision targeting with the potential for both therapeutic and diagnostic applications. By replacing traditional, bulky antibodies with more nimble minibinders, the team is addressing a key challenge in cancer treatment: the ability to effectively target and destroy tumor cells while minimizing harm to surrounding healthy tissue. This could represent a significant leap forward in reducing the side effects commonly associated with radiation therapy.
The use of machine learning to optimize minibinder design is particularly exciting. Historically, the process of designing proteins that can selectively bind to cancer cells has been highly labor-intensive and time-consuming. By streamlining this process through computational methods, Dr. Hicks and his colleagues are poised to accelerate the development of highly effective therapies, reducing both cost and time to market—a critical advantage in the race to develop new cancer treatments.
Moreover, the idea of dual-purpose radiolabeled minibinders that can both treat and diagnose cancer is intriguing. If the minibinders can be used in conjunction with PET imaging, this would open up new possibilities for real-time monitoring of tumor response to treatment, offering a level of precision that could significantly enhance clinical outcomes. The dual therapeutic-diagnostic function could also optimize the clinical workflow, making it more efficient and potentially reducing the need for multiple, separate diagnostic tests.
Despite the promise of this technology, there are some challenges ahead. The long-term safety and efficacy of these minibinders in humans will need to be rigorously tested, especially as they begin to be used in clinical settings. Furthermore, the development of a viable production process for these small proteins, which must be both efficient and scalable, could be a considerable obstacle. Minibinders are far smaller than antibodies, which could present new manufacturing complexities and regulatory hurdles, particularly in terms of ensuring that they are stable and safe for human use.
It will also be interesting to see how quickly the commercialization efforts move forward. Dr. Hicks’ plan to spin out a company from the IPD could be a smart move, but the success of this venture will depend heavily on securing further investment and navigating the often complex process of bringing a novel technology to market. The team’s ability to attract support from stakeholders, including both investors and regulatory bodies, will be crucial in determining how quickly this promising therapy reaches cancer patients.
In sum, while there is still much to be done before minibinder-based therapies can be widely available to patients, the combination of precision targeting, potential for dual functionality, and accelerated development through machine learning puts this research at the forefront of innovative cancer treatments. It will be fascinating to see how these technologies evolve and what impact they may have on cancer care in the near future.
