We were honored to be able to speak about the promise of immuno-oncology (IO) therapeutics at this year’s Molecular Med Tri-Con conference and the 12th Annual Biomarkers Congress. Bringing together thought leaders from around the world, including academics, pharma customers and therapeutic companies, these conferences are critical for the acceleration of precision health for improved treatment methods across a variety of disease-types.
We first presented at Tri-Con, in San Francisco, CA, before moving on to the UK to speak at Biomarkers Congress. Our talks focused on the need for ultra-sensitive measurement of protein biomarkers in IO therapeutics, and the role that our Simoa technology plays in furthering research in this area. As conferences that generally run the gamut in terms of topics related to molecular medicine and biomarkers, it was fascinating to see that IO was the topic of more than half of the presentations at both conferences.
IO therapies activate the body’s immune system to attack cancer cells. It’s proving to be a very powerful approach to treating late-stage cancers, and when patients have a positive response to IO therapies they have a higher chance of extended recovery in comparison to more traditional chemotherapeutic approaches. Biomarkers are incredibly important for the development and use of IO therapies, and are crucial in accelerating our understanding of the mechanism of action of these new treatments. They provide quantitative measures of patient response in clinical trials, lead to the development of companion diagnostics for targeted, personalized treatment, and enable quantitative monitoring of treatments to determine efficacy, overall immune response, adjust dosing, and other variables.
While a wide variety of biomarkers have shown promise for use in IO therapies, one of the challenges with using biomarkers is that there is no complete, comprehensive, known set of biomarkers that can be used to track and inform IO treatments. Therefore, it’s critical that we continue to unravel the complex biology so we can determine which specific biomarkers will be most informative. That’s where Simoa comes in. This single-molecule detection method makes protein measurements 1000 times more sensitive than traditional biomarker technologies, making it the perfect tool to measure subtle changes to the immune system or the activation of cancer specific markers.
Recent publications have shown the potential for Simoa to impact the ultra-sensitive detection of protein biomarkers important in IO. One key demonstration leveraged sensitivity to measure the amount of a cancer-specific protein biomarker in single cells. The cancers targeted by IO therapies are complex and characterized by heterogeneity in the tumor cell populations, so biomarker information at the single cell could prove invaluable. Dr. David Walt of Tufts University, and Quanterix’ technology founder, isolated single cells from two prostate cancer cell lines—one with a normal level of PSA expression and another that had been passaged many more times and only produced a very low level of PSA—lysed the cells in a small volume, and used Simoa to measure the concentration of PSA in individual cells. He found that Simoa was able to detect 12,000 PSA molecules per single cell, highlighting this as a simple, automated and precise way to quantitate a specific protein in a single cell. He showed that there was a large range of PSA concentrations within a specific subpopulation of cells, and that the distributions differed significantly between the two cancer cell lines. This work was published in Analytical Chemistry and demonstrated the potential to analyze the concentration of cancer biomarkers in single cells from tumors or in populations of specific immune cells.
Perhaps one of the most promising classes of biomarkers for IO treatments are cytokines. A study published in the Journal of Immunological Methods, used Simoa to measure cytokine levels in normal individuals and patients with clinically active Crohn’s disease (CDAI>220) undergoing anti-TNF-a therapy. We observed significant elevation of IL-6 in plasma from patients compared to controls. After therapy, the mean reduction in the concentrations of TNF-a and IL-6 were 46% and 58%, respectively. What we found was that changes in cytokine concentrations after therapy indicate that measurement using digital ELISA could be used for monitoring therapeutic efficacy. Simoa is the first technology to demonstrate the ability to measure changes in the concentration of these cytokines in blood, after administration of a specific biological therapeutic. This approach is being extended to cytokines important in IO therapies, for example, those in the interferon gamma activation pathway that is downstream of checkpoint inhibition. Being able to quantitatively measure the reduction in cytokine levels using Simoa, could be critical for the monitoring of immune responses that would be unattainable using standard methods.
Conferences like Tri-Con and Biomarkers Congress are particularly important as they help facilitate the sharing of information for the transformation of precision health. At the same time, they also highlight the long way we still have yet to go before we can realize the full potential of revolutionary approaches to treating cancer and other diseases. For example, we found that while there is significant interest in measuring relevant biomolecules, there is a lack of understanding about what it all means and how the information can be used to make more effective diagnoses. Places like our Accelerator Lab can be a vital tool in helping accelerate research across all therapeutic categories, including traditional oncology and IO approaches. This innovation center can help bolster biomarker research, custom assay development and clinical sample testing for improved diagnostics and treatment methods. We invite you to check it out and see what you might be able to discover.