Author(s):
ACCCBuzz spoke with Fox Chase Cancer Center to learn more about its partnership with Omniscope, a leader in advanced molecular profiling technology, in hopes of developing an assay that accurately predicts which patients will respond well to immunotherapy based on the presence of certain T-cell clones.
As cancer care grows increasingly precise, research is prioritizing targeted treatments that are not only highly effective, but tailored to individual patients with, ideally, minimal adverse effects (AEs). Non–small cell lung cancer (NSCLC) is one such case. After the discovery of PD-1 and PD-L1—proteins on certain T cells—in the early 2000s, the development of immune checkpoint inhibitors (ICIs) changed the landscape of NSCLC treatment. Namely, the use of ICIs boosts the immune response against cancer cells, in some cases shrinking tumors or slowing their growth.
However, not all patients respond to immunotherapy, and over 20% experience significant immune-related adverse events (irAEs) that disrupt their quality of life. Given the risk of irAEs, biomarker testing has become instrumental in determining which patients are most likely to benefit from immunotherapy. That said, existing assays are not perfect, so there is a continued need for a more accurate means of predicting which patients will respond most favorably to this treatment.
Acutely aware of this challenge, Hossein Borghaei, DO, MS, chief of Thoracic Medical Oncology and professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, has spearheaded a partnership between Fox Chase and Omniscope, a leader in advanced molecular profiling technology. Dr. Borghaei first connected with Omniscope at the European Society for Medical Oncology (ESMO) conference in Madrid, where Omniscope representatives presented an abstract on their work in isolating T-cell receptors.
“T cells come in a variety of subtypes, and Omniscope had developed this really interesting technique where, from a small amount of blood, they could isolate specific T-cell receptors as they evolve in the course of a certain treatment,” Dr. Borghaei explained. These changes in the T-cell repertoire from patient to patient may be indicative of whether a person will respond well to a specific type of immunotherapy—key information for treatment planning.
After meeting with the team from Omniscope, an agreement was reached to leverage their proprietary T-cell profiling platform to analyze a prospective study led by Fox Chase on immunotherapy-induced T-cell dynamics in NSCLC. Fox Chase plans to enroll about 100 patients with an NSCLC diagnosis who will receive a form of immunotherapy, either alone or in combination with chemotherapy. Blood samples will be collected at 5 to 6 time points to isolate the T cells, which will be sent to Omniscope for sequencing. The data will then be returned to statisticians at Fox Chase for analysis with participants’ clinical responses.
“The simple question for us will be whether there are T-cell clones in these patients that are associated with responsiveness to immunotherapy,” said Dr. Borghaei. “If so, which one of the clones, and when do they emerge in the course of treatment?” In addition, the study will examine changes in T-cell receptors over time in response to certain treatments.
Few existing studies have specifically examined dynamic change in T-cell receptors. And while Omniscope is not the only company to broach molecular profiling, its ability to track T-cell clones over time with just a small amount of blood is novel. “This is normally very expensive to do, especially with the number of patients we’re working with,” said Dr. Borghaei, “but the way [Omniscope] has managed to do it has brought costs down and made this project a lot more feasible.”
The overarching, long-term goal of both the study and partnership is to develop an assay that accurately predicts which patients will respond well to immunotherapy. While that aspiration will likely not be achieved quickly and may require more than 1 assay or test, Dr. Borghaei is hopeful that findings from this study will contribute significantly to oncologists’ understanding of T-cell repertoire changes over time.
“Beyond having an assay, I’m hoping that we will learn, for example, that specific T-cell subclones are really important for an immune response,” Dr. Borghaei explained. “That alone can have significant downstream effects in terms of further research, because then we can go down the route of investigating how we can ensure every patient has a particular sort of T-cell clone.” This enhanced understanding of tumor cell biology has the potential to build the foundational knowledge required to make the immune system more robust when fighting cancer.
The partnership between Fox Chase and Omniscope is proof of the importance of interdisciplinary collaboration and connection among health care providers. Meetings like ESMO are an important forum for clinicians, scientists, and technicians to share ideas, discuss challenges they are facing, and work toward innovative solutions that will shape the future of oncology. “To me, this experience highlights the importance of presenting data [at conferences] and interacting with each other. You never know what kind of projects could come out of it and how patients will benefit from it,” reflected Dr. Borghaei.
To exchange and explore quality and process improvements in cancer care with members of the entire multidisciplinary care team, join ACCC on October 21–23 in Boston, Massachusetts, for the 43rd National Oncology Conference. Register before July 31 to secure your early bird discount, and watch highlights from last year’s event here.
