As one of three Tactical Research Projects funded by the NZ RNA Platform this year, Dr Rachel Perret's research is exploring how RNA technology could transform the future of CAR T-cell therapy. By combining the Malaghan lnstitute's expertise in cellular immunotherapy with the Platform's growing RNA and LNP capability, the project is exploring a new approach to developing CAR T-cells – known as RENTAL CARs – that could make them faster to produce, safer and applicable to more diseases.
This proof-of-concept study highlights how the Platform is supporting innovative, high-impact research with strong potential for clinical translation in Aotearoa New Zealand.
How can RNA technology be harnessed to expand and improve CAR T-cell therapies?
Chimeric antigen receptor (CAR) T-cell therapy works by engineering a patient's immune cells to recognise and destroy cancer cells. While this approach has transformed treatment for certain blood cancers, research is ongoing to improve the safety and efficacy of this ground-breaking immunotherapy and expand it to other cancers and diseases.
In her work at the Malaghan Institute, Dr Perret is developing new ways to engineer CART-cells to function more safely and efficiently. One area of her work is the exploration of RNA-based CART-cells (RENTAL CARs). Unlike conventional CART therapies that permanently modify immune cells, RNA approaches produce temporary CART-cells that function for a limited time before naturally disappearing.
This strategy may lend itself to treating autoimmune disorders where temporary immune cell programming is preferable to long-term modification, while simplifying the production of these therapies and reducing long-term risks.
RNA platform acceleration opportunity
The national RNA platform has provided a Tactical Research Grant to support early feasibility work on RNA based CART-cells. This one year project brings together the Malaghan lnstitute's CART clinical platform and the national RNA platform to optimise RNA and LNP design for use in CART-cells manufactured in the laboratory.
What the future holds
This initial proof of concept study is intended to act as a catalyst for a larger research programme focused on translating RENTAL CART-cells into the clinic. The first step will be to produce these in the laboratory as personalised therapies, and to evaluate their safety and efficacy in patients with severe forms of lupus.
Over time, the goal is to further adapt this approach to create off-the-shelf RENTAL CAR formulations that could be delivered like a vaccine. This would significantly broaden access and unlock a wide range of applications, from autoimmune disease to blood cancers and beyond.
For more info about Rachel's project
