A new test developed by researchers at Duke-NUS allows for the real-time observation of T cells that have been modified to combat cancer after they are reintroduced into a cancer patient’s body. This straightforward and groundbreaking test gives doctors the ability to monitor the performance of these cancer-fighting cells throughout the treatment process.
T cells, part of the immune system, are responsible for identifying and eliminating cells infected by viruses, bacteria, and cancerous cells. Initially created to identify T cells specific to SARS-CoV-2, this technology has now been repurposed for applications in cancer immunotherapy. The test, which requires only a small sample of blood (less than a quarter teaspoon), functions by activating the targeted T cells in the blood, prompting them to release chemical signals known as cytokines. This allows for the assessment of both the quantity and functionality of these targeted T cells.
In a proof-of-concept study published in Immunotherapy Advances, the research team introduced specific fragments called peptides that stimulate the T cells engineered to combat liver cancer associated with the Hepatitis B virus in treated patients. Their test was used to evaluate whether these engineered T cells persisted in the bloodstream and continued to function effectively after being infused into the patient.
Assistant Professor Anthony Tan from Duke-NUS’ Emerging Infectious Diseases Programme and first author of the study remarked:
“Our innovative test allows for rapid detection and analysis of engineered T cells in patient blood samples. Its simplicity and speed could greatly influence the clinical field by making advanced treatments more widely available.”
As engineered T-cell therapies gain popularity for treating cancers such as Hepatitis B virus-related liver cancer and various blood cancers, it’s essential to accurately and effortlessly monitor how these engineered cells perform in patients over time to evaluate the effectiveness of these treatments.
This adaptable technology can also help expedite the translation of new T-cell therapies from research settings to patient treatments. The research team has already shown that the test can be modified for several viral infections, marking their first application in cancer therapies, where it can be utilized for harnessing T-cell receptor (TCR) engineered T cells and chimeric antigen receptor (CAR) T-cell therapies.
Professor Antonio Bertoletti from Duke-NUS Emerging Infectious Diseases Programme, who is the senior author of the study, stated:
“Monitoring the functionality of adoptively transferred engineered T-cell products can yield vital insights regarding treatment effectiveness overtime, an area that remains predominantly unexplored. We anticipate that this proof-of-concept can help accelerate research into other CAR and TCR T-cell therapies and assist clinicians caring for patients undergoing these innovative treatments.”
In collaboration with Lion TCR Pte Ltd, the test has been utilized in a clinical trial for Hepatitis B virus-TCR T-cell therapy called the SAFE-T-HBV trial, which investigates the efficacy of a new therapy on two patients and showcases the test’s role in enhancing precision in immunotherapy results.
The research team is eager to progress this proof-of-concept via larger-scale clinical studies.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, sees immense potential in this new test. He expressed:
“This innovation represents not just progress in cancer treatment, but a major leap in patient care that could have implications for multiple diseases. By providing clinicians with real-time insights into the functionality of these engineered T cells, we’re setting the stage for highly personalized treatment strategies that may significantly improve patient outcomes.”
Duke-NUS is a leader in biomedical research, combining fundamental scientific research with applicable innovations to develop treatment methods and diagnostic tools aimed at improving health worldwide.
This research has been supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, and MOH Holdings Pte Ltd under the NMRC Singapore Translational Research Investigator Award (MOH-000019). The SAFE-T-HBV clinical trial was sponsored by Lion TCR Pte Ltd.
