by Duke-NUS Medical School

T cells are removed from the patient's body, engineered to fight disease, then infused back into the patient's bloodstream. At the point of infusion, and at various time points after, blood is drawn to monitor the efficacy of the T-cell therapy. Credit: Duke-NUS Medical School

A novel test developed by Duke-NUS researchers enables real-time monitoring of T cells that have been engineered to fight cancer after re-introduction into the body of a cancer patient. This simple and innovative test provides clinicians with the ability to track the function of these cancer-fighting cells over the course of the treatment.

T cells are a type of immune cell that seeks out and destroys cells infected by viruses, bacteria as well as tumor cells. Originally designed to detect SARS-CoV-2-specific T cells, this technology has now been adapted for use in cancer immunotherapy applications.

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.

In this proof-of-concept study, which was published in Immunotherapy Advances, the research team introduced fragments, called peptides, that stimulate the T cells engineered to fight Hepatitis B virus-related liver cancer present in the treated patients.

Using their test, they assessed whether the engineered T cells remained in the blood and continued to function properly after infusion into the patient.

Assistant Professor Anthony Tan, from Duke-NUS' Emerging Infectious Diseases Program and first author of the study, commented, "Our innovative test enables us to swiftly 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."

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.

(From left to right) Assistant Professor Anthony Tan, PhD student He Shan and Professor Antonio Bertoletti monitor the effectiveness of T-cell immunotherapy using their newly developed test. Credit: Duke-NUS Medical School

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 patient's 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.

Professor Antonio Bertoletti, from Duke-NUS Emerging Infectious Diseases Program and senior author of the study, added, "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.

"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 Pte Ltd, 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 this proof-of-concept through larger clinical studies.

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, said that he sees potential in the new test. He added, "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.

"By offering clinicians real-time data on the functionality of these engineered T cells, we are paving the way for highly personalized treatment strategies that could significantly enhance patient outcomes."

More information: Anthony T Tan et al, A rapid method to assess the in vivo multi-functionality of adoptively transferred engineered TCR T cells, Immunotherapy Advances (2024). DOI: 10.1093/immadv/ltae007

Provided by Duke-NUS Medical School