Plug-and-play test evaluates T cell immunotherapy effectiveness

A novel test developed at Duke-NUS Medical School enables real-time monitoring of T cells that have been engineered to fight cancer, after reintroduction into the body of a cancer patient. The test provides clinicians with the ability to track the function of these cancer-fighting cells over the course of the treatment.

The test, which uses less than a quarter teaspoon of blood, works by stimulating the 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. Originally designed to detect SARS-CoV-2-specific T cells, the technology has now been adapted for use in cancer immunotherapy applications.

In a proof-of-concept study, published in the journal Immunotherapy Advances, the research team introduced fragments, called peptides, which stimulate the T cells engineered to fight hepatitis B virus-related liver cancer present in the treated patients. Using their test, the team assessed whether the engineered T cells remained in the blood and continued to function properly after infusion into the patient.

“Our innovative test enables us to swiftly detect and analyse engineered T cells in patient blood samples,” said Assistant Professor Anthony Tan, first author on the study. “Its simplicity and speed could have a significant impact on the clinical field helping to make advanced treatments more accessible.”

With engineered T-cell therapies becoming more widely used to treat malignancies, including hepatitis B virus-induced liver cancer and a range of blood cancers, being able to accurately and easily track how these engineered cells behave in the body over time will be crucial in monitoring the effectiveness of these therapies in individual patients. At the same time, the plug-and-play concept can help accelerate the translation of new T-cell-based therapies from the laboratory to patient bedside. The research team has already demonstrated 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 harnessed for T-cell receptor (TCR) engineered T cells as well as chimeric antigen receptor (CAR) T-cell therapies.

“Tracking the functionality of adoptively transferred engineered T-cell products could provide important information on treatment efficacy over time, an assessment which at the moment remains largely unexplored,” said Professor Antonio Bertoletti, senior author on the study. “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 clinicians on the frontline caring for patients receiving these novel therapies.”

In collaboration with Lion TCR, the test has been deployed in a hepatitis B virus-TCR T-cell therapy clinical trial, called the SAFE-T-HBV trial, evaluating the effectiveness of a novel therapy in two patients and demonstrating the test’s impact on improving the precision of immunotherapy outcomes. The team is now looking to advance the proof-of-concept through larger clinical studies.

“This innovation isn’t just a step forward in cancer therapy; it’s a significant advancement in patient care that could extend across multiple diseases,” said Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS. “By offering clinicians real-time data on the functionality of these engineered T cells, we are paving the way for highly personalised treatment strategies that could significantly enhance patient outcomes.”

Image caption: Assistant Professor Anthony Tan, PhD student He Shan and Professor Antonio Bertoletti monitor the effectiveness of T-cell immunotherapy using their newly developed test. Image credit: Duke-NUS Medical School.