Advanced proteomics tools bring us one step closer to precision medicine

Proteomics is becoming an increasingly important tool in biopharmaceutical development and is key to advancing precision medicine, which has the power to revolutionize healthcare and treat many complex diseases that are currently lacking effective treatment like Parkinson’s and non-small cell lung cancer. Advancements in proteomics technology are enabling scientists to gain a deeper understanding of individual physiology and the intricate molecular mechanisms underlying disease. The latest protein microarray tools have ushered in a new era of precision, which allows for the more precise detection of early disease presence. Plus, these tools have also helped identify novel disease biomarkers, and assess the safety and effectiveness of emerging personalized medications.

One expert contributing to the precision medicine mission is Fredrik Sundberg, Vice President of Markets and Business Development at Sengenics. Sengenics utilizes advanced proteomic tools to provide personalized and precise insights into patients’ humoral immune system with the aim of developing more targeted treatment strategies. Sundberg takes proactive steps in overseeing strategic partnerships and collaborations with many academic institutions, biopharmaceutical companies, and other key stakeholders within the field of oncology, autoimmune disease, and neurological disorders. These efforts are dedicated to the development of groundbreaking biopharmaceuticals with enormous potential to save lives.

In this article, Sundberg discusses the current landscape of precision medicine and explains why protein microarrays are essential tools in the development of personalized therapies. He also explores the current challenges biopharmaceutical scientists face when it comes to conducting immunoassays, and how Sengenics' i-Ome^® Discovery protein microarray can help overcome these challenges and advance the field of biomarker discovery for the better.

Precision medicine is a work in progress

The biopharmaceutical industry is experiencing significant transformation, with the emergence of complex drug modalities, such as bispecifics, immunoconjugates, and mRNA. Proteomics involves the study of the interactions, function, composition, and structures of proteins and their cellular activities. It plays a vital role in biopharmaceutical research and drug development as it provides unique insights into the pathogenesis of disease at the protein level where disease actually occurs, consequently uncovering important biomarkers. This knowledge paves the way for the development of novel targeted therapies and precision medicine.

Precision medicine involves customizing medical treatments for individual patients, considering their distinct molecular profile (genomic, proteomic, metabolomic, etc.), as well as environmental and lifestyle factors. This approach is designed to enhance patient outcomes through optimization. Nevertheless, the pursuit of precision medicine and personalized treatments is still a work in progress.

Doctors today prescribe personalized medicine by tailoring treatments based on diagnostics, especially in cases like cancer, where specific antibody medicines are used. However, there are limitations to this approach and there are still a limited number of treatment options available. A key challenge is the lack of understanding differing degrees of patient responses to the same treatment. It is important to recognize that not all medications prove effective for every individual, and the underlying reasons for this variability frequently remain unclear.

Sundberg comments, “To advance precision medicine, we need to develop new tools and diagnostics that can provide deeper insights to better understand the patient, such as more advanced proteomics technology. Whilst genomics can provide valuable information about health and disease to inform precision medicine, it only offers part of the puzzle. Combining genetic studies with proteomics is key, as proteins and antibodies reveal essential information about a person's individual physiology, helping fill in the gaps.”

Protein microarrays are crucial for developing personalized treatments

Protein microarrays are powerful high-throughput tools used in biopharmaceutical research to aid in the advancement of personalized medicine. These tools consist of a solid surface, such as a glass slide or microarray chip, where thousands of different immobilized proteins and antigens are bound. A biological sample, often containing proteins or other molecules from cells, tissues, or bodily fluids (such as serum or plasma) are then applied to the array. If any proteins or antibodies within the sample interact with the immobilized antigens on the array, they bind together. The most common case is patient serum antibodies binding specifically with cognate antigens on the microarray. Researchers can use these microarrays to simultaneously study the presence, interactions, and activities of proteins and antibodies, making them valuable for tasks such as identifying disease biomarkers, studying protein function, and assessing drug interactions.

“A perfect example of where protein microarrays are invaluable is the study of autoantibodies. Autoantibodies are the result of the humoral immune system identifying disease relevant changes, they are a highly, biologically relevant marker. Autoantibodies can also interact with an individual's own proteins and can cause various autoimmune diseases. Autoantibodies are often present before any other symptoms appear and are an early indicator of disease. Protein microarrays can be used for autoantibody profiling, which can help with earlier disease diagnosis and treatment. They can also assist with drug development and provide an in-depth assessment of treatment responses,” says Sundberg.

Sundberg continues, “However, scientists performing microarrays and other information-rich biophysical tools, and the biopharma industry in general, face several challenges that can delay the progress of developing novel personalized drugs. These need to be addressed for us to progress and ensure we are conducting these assays as effectively and efficiently as possible.”

Data overload presents a major challenge in proteomics

Generating and interpreting high-quality analytical data is essential throughout the drug development lifecycle and influences regulatory drug submissions. “Despite the benefits of automation and modern analytics, high-throughput proteomics tools generate vast amounts of data, which doesn’t always align neatly with genomics data. This leads to an avalanche of data and difficulties in data integration and interpretation,” Sundberg explains. “Whilst digital solutions like cloud computing, AI, and machine learning help improve efficiency, drug development remains a lengthy and costly process, with drug failures still mainly attributed to safety and efficacy issues.”

High reproducibility, specificity and sensitivity are essential

Sundberg elaborates on the additional challenges associated with protein microarrays, emphasizing the importance of reproducibility, specificity, and sensitivity. When conducting analytical assays, it is crucial to ensure that the data generated are consistently accurate. A lack of standardization in the use of analytical tools and assay procedures can pose problems for reproducibility and result in inconsistency, which prevents drugs from progressing to the next stage of development.

Protein microarrays must also be able to accurately identify only the proteins of interest. This is difficult with complex sample matrices that contain a wide range of proteins, and potentially unfolded proteins on the chip surface. This could result in non-specific binding. It is critical that proteins on the chip retain their tertiary structure on the planar surface and do not bleed into neighboring proteins, thus resulting in background noise or interfering with antibody-antigen binding.

Sundberg explains, “Effective microarrays also need to be sensitive enough to be able to detect even trace amounts of antibodies ensuring that no potentially relevant biomarkers are missed. The inherent heterogeneity within patient populations can also make it difficult to identify consistent and reliable biomarkers universally, as not all individuals will exhibit the same protein profiles or responses to treatments.”

Mastering protein microarray challenges

Sengenics is committed to advancing precision medicine through its unique proteomics technology, known as i-Ome^® Discovery Protein Microarray. This powerful tool has been designed to enable highly specific, high-density autoantibody profiling, which, in turn, streamline the biomarker discovery process. This array features a curated panel of more than 1,800 biologically relevant proteins and employs KREX^™ protein folding technology to ensure only correctly folded, functional proteins, are immobilized on the array surface. This feature minimizes unwanted noise from non-relevant antigens and non-specific binding, and results in highly specific and reproducible data.

Sundberg states, “The i-Ome Discovery Protein Microarray can help address the challenges, either by speeding up existing processes or by fundamentally improving the quality of data to enhance reliability and increase the likelihood of success in clinical stages. With this technology, it is possible to reduce late-stage attrition and lower costs by identifying more reliable and clinically relevant biomarkers that can accurately determine responsive patients and those at risk of adverse events.”

The i-Ome Discovery also significantly enhances the process of patient stratification by delving into the patient's humoral immune system and pinpointing relevant autoantibody biomarkers. This enables the categorization of patients with unparalleled accuracy, ensuring personalized treatment strategies can be tailored to their unique disease profiles.

Sundberg emphasizes that it is important to work collaboratively to help manage and make sense of the data generated with protein microarrays. He says, “Our team of highly trained and knowledgeable laboratory scientists and bioinformaticians are also on hand to help guide customers in the identification of key autoantibodies and interpretation of data.”

Precision medicine will one day be a reality

Sundberg believes the future of proteomics holds tremendous promise for unlocking the full potential of precision medicine. However, for this to occur, scientists must find new and important indicators that can greatly improve the early detection of diseases and the creation of customized treatments. Such advancements are especially critical for complex conditions, such as cancer, neurological disorders, and various autoimmune diseases that lack effective treatments.

Sundberg concludes, “I hope that companies, research institutes, and academia will adopt innovative technologies and collaborative approaches to scale novel therapies, particularly for unmet medical needs. This concerted effort could lead to improved global access to life-saving drugs. I know there is still a lot of work to be done, but I am positive that success is achievable.”