Growing young ‘warriors’ to fight cancer

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SGH team develops platform to manufacture special T-cells to fight a variety of cancers, with early study showing promise

Dr Cheung uses a pipette to transfer cord blood cells into a culture container in the sterile biosafety cabinet.

A TYPE of white blood cell, gamma delta T-cells (GDTcells), derived from cord blood, may be able to prevent or delay some cancer relapses, early studies by a team of Singapore General Hospital (SGH) researchers have shown.

The team also found that a platform they developed was able to generate these cells on a large scale.

The team is looking to put their findings to further test in a phase 1 clinical trial for leukaemia and lymphoma treatments.

“We are working closely with the Advanced Cell Therapy and Research Institute (the national cell therapy facility, ACTRIS) to validate and finalise Good Manufacturing Practices workflows,” said Dr Alice Cheung, Junior Principal Investigator, Department of Haematology, SGH, and senior author of the study.

The findings of the study were published in a peer-reviewed journal, Science Advances, in June 2023, she added.

T-cells are a type of white blood cells that help the body’s immune system fight germs and protect it from disease. GDT-cells, a subtype T-cell useful in cancer immunotherapy, have antiviral and antitumour properties that allow them to keep a look out for signs of biological stress, like cancerous or infected cells in the body, and are one of the first lines of defence against disease. GDT-cells can be found in the blood of an adult.

However, umbilical cord blood has greater enrichment of specific, more cytotoxic, subsets of GDT-cells, said Dr Cheung.

“Most initial efforts have been focused on exploring the use of GDT-cells in adults as cancer treatment. Unfortunately, response rates in early clinical trials were generally low and treatment efficacies were sub-optimal. This was why we decided to turn our attention to umbilical cord blood instead,” said Dr Cheung.

Dr Cheung puts the cell container into the incubator at 37°C.

The team from the Haematology and Molecular Pathology departments used more than 20 clinical grade umbilical cord blood samples from the Singapore Cord Blood Bank to produce and validate the GDT-cells on the platform, she said.

According to Associate Professor Goh Yeow Tee, Senior Consultant, Department of Haematology, SGH, “Umbilical cord blood-derived GDT-cells are akin to young warriors, potentially having longer-lasting effects and being more adaptable to take on additional functions.”

However, Assoc Prof Goh, also an author of the study, noted that the cord blood cells “are currently under-utilised, with the main concern that there may not be enough of these T-cells for clinical application, but our study has shown that it is potentially feasible”.

The study found that the cord blood GDT-cells that were manufactured on the platform were “potent cancer killers that were able to target a variety of solid and liquid cancers”, said Dr Cheung.

“These cell products are highly versatile, and can be combined with different existing cancer drugs such as small molecule drugs and antibodies to induce much higher cancer cell kill,” she added.

The platform, which uses the team’s proprietary technology, is able to produce massive amounts of various cancer-targeting GDT-cells quickly — in under two weeks. The cell products can then be frozen for storage, and thawed when needed for cancer treatment.

“Such cost-efficient production of off-the-shelf cancer immunotherapeutic cell products has the potential to deliver effective and affordable cancer treatment to patients in a timely manner,” added Dr Cheung.