Clinician-led approach could give doctors a control dial for cell therapies

by Walter and Eliza Hall Institute

edited by Sadie Harley, reviewed by Andrew Zinin

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An Australian clinician-led research team has developed a gene-editing platform that could give doctors more control over cell therapies, making them more practical for patients with complex immune conditions.

The new approach using prime editing could allow clinicians to use existing immune-suppressing drugs as a 'control dial' for cell therapies and help corrected cells survive in the body.

The WEHI-led research, published in Blood, aims to make cell and gene therapies more feasible for people who need ongoing immunosuppression, including those with rare immune disorders, organ or stem cell transplant recipients and patients receiving cell therapies for cancer.

Making cell therapies controllable

Cell and gene therapies often involve taking a patient's immune cells, correcting or engineering them in the lab and returning them to the body. But once those cells are back in the patient, clinicians have limited ways to selectively boost or suppress them.

This is particularly challenging for people who need ongoing immunosuppression, including some patients with rare immune disorders, transplants, severe infections or cancers linked to immune suppression.

The drugs needed to control disease or protect a transplanted organ can also suppress the therapeutic cells that the patient needs.

Co-senior author Dr. Miles Horton said the team used prime editing, an emerging gene-editing technology that can make precise DNA changes, to address a practical problem seen in clinical care.

"We've used genetic engineering to rewire these cells so clinicians could use existing drugs, already sitting in the hospital pharmacy, as a control dial," said Horton, a WEHI researcher and pediatrics resident at the Royal Children's Hospital.

"Some approaches being explored elsewhere would require doctors to adopt a new cell therapy and a new drug at the same time. Our aim was to build a platform around clinical reality, using medicines that clinicians already know and use."

The team showed T cells could be made resistant to a commonly used immunosuppressive drug (tacrolimus), while remaining sensitive to a related alternative (cyclosporin).

This precise 'control dial' could allow clinicians to use one drug to help corrected cells survive while other immune cells are suppressed, while preserving another drug option if the edited cells behaved unexpectedly and needed to be scaled back.

Built for clinical reality

The study focused on a rare and serious immune-related blood cancer that can affect children and young adults, subcutaneous panniculitis-like T-cell lymphoma with HLH, or SPTCL-HLH.

Using cells from people with the disease, researchers used prime editing to correct a disease-causing mutation and add a second edit that made the corrected cells resistant to the drug tacrolimus.

The same platform was then tested in other types of cell therapy, including virus-specific T cells that could one day help transplant recipients fight infection without stopping anti-rejection drugs, and CAR T cells used in cancer treatment.

Co-senior author Dr. Tom Lew said the work was designed around clinical needs.

"As clinicians, we are always thinking about whether a promising technology could realistically fit into patient care," said Lew, a WEHI researcher who is also a clinical hematologist at Peter MacCallum Cancer Center (Peter Mac) and the Royal Melbourne Hospital (RMH).

"Our approach is built around medicines that are already part of routine clinical practice, which could make translation more practical."

First author Dr. Esther Bandala-Sanchez said the platform was designed to be precise and adaptable.

"We showed this strategy could be applied across different types of therapeutic T cells, not just one disease setting," Bandala-Sanchez said.

"The edited cells stayed functional under immunosuppression, and importantly, remained sensitive to other drugs.

"That precision is what makes the platform so promising as a foundation for future cell therapies."

The team is now working toward a first-in-human trial.

Publication details

Esther Bandala-Sanchez et al., Prime editing enables drug-controllable T-cell therapies with clinical immunosuppression, Blood Journal (2026). DOI: 10.1182/blood.2026033156

Journal information: Blood

Key medical concepts

T-LymphocytesTacrolimusCyclosporine

Clinical categories

OncologyAllergy and immunology Provided by Walter and Eliza Hall Institute Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

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