Researchers explore 'RENTAL CAR' approach to CAR T-cell therapy

The collaboration, led by the Malaghan Institute's Professor Robert Weinkove and Dr Rachel Perret, is being supported by an RNA Development Platform Tactical Research Grant, designed to offer short, focused investment to generate proof-of-concept data. 

“RNA technologies offer the potential to produce CAR T-cells quicker with fewer long-term risks than current therapies,” says Dr Perret. “These approaches may also extend CAR T-cell therapies beyond cancer to autoimmune diseases such as lupus – conditions where you want to eliminate a specific harmful immune response, not permanently alter the immune system.”

Nicknamed ‘RENTAL CARs’ – these engineered cells are designed to disappear naturally from the body once their mission is complete.  Rather than permanently rewriting a cell’s instructions, RNA acts as a temporary message – like a Post-It note instead of a tattoo. The cell carries out its task, the message degrades, and the modification disappears.

Over the next year, the team will optimise RNA design and delivery systems to lay the groundwork for future development.

“For some conditions, temporary immune cell programming with RNA might be preferable to long-term modification,” says Prof Weinkove. “This laboratory project combines new chemistry, new immune cell targeting methods, and new RNA designs. It could open up genuinely new clinical possibilities.”

Future applications of this technology could include severe autoimmune diseases such as lupus, where precisely targeted and reversible immune reprogramming could offer significant advantages over current treatments. Longer term, the team aim to develop ‘off-the-shelf’ RENTAL CAR therapies that could be delivered like a vaccine, removing the need for each treatment to be individually manufactured from a patient’s own cells, dramatically expanding access to the treatment.

“This study is intended to act as a catalyst for a larger research programme and future funding,” says Dr Perret. “Growing our ability to design and use RNA CAR T technologies will allow us to develop new immunotherapies for a range of diseases – therapies that could be safer, more accessible, and more affordable than those available today.”