A new test developed by Duke-NUS researchers allows real-time monitoring of T cells that have been engineered to fight cancer, after their reintroduction into the body of a cancer patient. This simple and innovative test gives doctors the ability to track the function of these cancer-fighting cells over the course of treatment.
T cells are a type of immune cell that seeks out and destroys cells infected by viruses, bacteria, and tumor cells. This technology, originally designed to detect SARS-CoV-2-specific T cells, has now been adapted for use in cancer immunotherapy applications. The test, which uses less than a quarter teaspoon of blood, works by stimulating target T cells in the blood to release chemical signals, called cytokines, through which the quantity and quality of the target T cells can be measured.
In this proof-of-concept study, which was published in Advances in immunotherapy,The research team introduced fragments, called peptides, that stimulate T cells designed to fight hepatitis B virus-related liver cancer present in treated patients. Using their test, they evaluated whether the modified T cells remained in the blood and continued to function properly after infusion into the patient.
Assistant Professor Anthony Tan, from the Duke-NUS Emerging Infectious Diseases Program and first author of the study, commented:
“Our innovative test allows us to rapidly detect and analyze engineered T cells in patient blood samples. Its simplicity and speed could have a significant impact on the clinical field, helping to make advanced treatments more accessible.”
As engineered T cell therapies are increasingly used to treat malignancies, including hepatitis B virus-induced liver cancer and a variety of blood cancers, it will be crucial to be able to accurately and easily track how These engineered cells behave in the body over time. monitor the effectiveness of these therapies in individual patients.
At the same time, this plug-and-play concept can help accelerate the translation of new T cell-based therapies from the laboratory to the bedside. The research team has already shown that the test can be adapted for use in numerous viral infections, but this is their first foray into cancer therapies, where the test can be leveraged for T cells modified with T cell receptors (TCR). ), as well as for chimeric antigen receptor (CAR) T cell therapies.
Professor Antonio Bertoletti, from the Duke-NUS Emerging Infectious Diseases Program and lead author of the study, added:
“Monitoring the functionality of engineered T cell products through adoptive transfer could provide important information on treatment efficacy over time, an assessment that at the moment remains largely unexplored. We hope that with this proof of concept “We can help accelerate research into other CAR and TCR T cell therapies, as well as support front-line clinicians caring for patients receiving these new therapies.”
In collaboration with Lion TCR Pte Ltd, the test has been implemented in a hepatitis B virus TCR T cell therapy clinical trial, called the SAFE-T-HBV trial, evaluating the efficacy of a new therapy in two patients and demonstrates the effectiveness of the test. impact on improving the precision of immunotherapy results.
The team now seeks to advance this proof of concept through larger clinical studies.
Professor Patrick Tan, senior vice dean for research at Duke-NUS, said he sees potential in the new test. He added:
“This innovation is not only a step forward in cancer therapy, it is a significant advance in patient care that could be extended to multiple diseases. By offering doctors real-time data on the functionality of these engineered T cells, “We are paving the way for highly personalized treatment strategies that could significantly improve patient outcomes.”
As a leader in biomedical research, Duke-NUS combines basic scientific research with translational applications to innovate treatment approaches and diagnostic tools to promote global health.
This research is supported by the Ministry of Health, Singapore through the Office of the National Medical Research Council (NMRC), 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.