Arovella Therapeutics has demonstrated that its novel CLDN18.2-targeting CAR incorporated into iNKT cells effectively eliminates pancreatic and gastric cancer cells in vitro, with IL-12-TM armouring enhancing potency and durability.
- CLDN18.2 CAR-iNKT cells effectively kill pancreatic and gastric cancer cells in vitro
- IL-12-TM armouring boosts CAR-iNKT cell expansion and tumour control
- Armoured CAR-iNKT cells maintain high cytotoxicity over four serial tumour challenges
- Data supports advancing to in vivo mouse models for solid tumour testing
- CLDN18.2 is a validated target with growing commercial interest
A Promising Advance in Solid Tumour Immunotherapy
Arovella Therapeutics Ltd (ASX:ALA) has revealed encouraging preclinical data showcasing the effectiveness of its innovative chimeric antigen receptor (CAR) technology targeting CLDN18.2, a protein highly expressed on pancreatic and gastric cancer cells. By engineering invariant natural killer T (iNKT) cells with this CAR, the company demonstrated robust killing of cancer cells in laboratory assays, a critical step forward in its immuno-oncology pipeline.
CLDN18.2 is an attractive therapeutic target due to its selective expression on tumour cells in these cancers, which are notoriously difficult to treat and have high mortality rates globally. Arovella’s approach leverages iNKT cells, a unique immune cell type, modified to express the CLDN18.2 CAR, enabling precise recognition and destruction of cancer cells.
Enhancing Potency with IL-12-TM Armouring
What sets this study apart is the incorporation of IL-12-TM, a membrane-bound cytokine designed to ‘armour’ the CAR-iNKT cells. This addition significantly enhanced the cells’ expansion and sustained tumour-killing ability across multiple rounds of cancer cell challenges. The armoured CAR-iNKT cells maintained over 97% killing efficiency against pancreatic cancer cells and 82% against gastric cancer cells after four successive tumour challenges, indicating durable and potent anti-tumour activity.
These findings, generated under the guidance of Professor Gianpietro Dotti at the University of North Carolina, suggest that IL-12-TM armouring could overcome common hurdles in solid tumour immunotherapy, such as immune cell exhaustion and limited persistence.
Implications and Next Steps
CEO Dr Michael Baker highlighted the significance of these results as a milestone for Arovella’s expansion into solid tumours. The data not only validate the functionality of the CLDN18.2 CAR but also demonstrate the added value of cytokine armouring technology in enhancing therapeutic durability.
Looking ahead, Arovella plans to advance these CAR-iNKT cells into in vivo mouse models of pancreatic and gastric cancer to further assess efficacy and safety. Success in these models would pave the way for clinical development, potentially addressing a substantial unmet need in oncology.
The CLDN18.2-targeting space is gaining momentum, with existing therapies like Zolbetuximab already approved in Japan and the US, and the market projected to exceed $800 million by 2030. Arovella’s novel CAR-iNKT platform, combined with IL-12-TM armouring, positions it as a compelling contender in this evolving landscape.
Bottom Line?
Arovella’s data mark a promising step toward durable CAR-iNKT therapies for tough solid tumours, with eyes now on in vivo validation.
Questions in the middle?
- How will the armoured CAR-iNKT cells perform in animal models and eventual clinical trials?
- What safety profile will the IL-12-TM armouring exhibit in vivo, given cytokine-related risks?
- How does Arovella’s approach compare to existing CLDN18.2-targeted therapies in efficacy and scalability?