Melbourne-based biotechnology company Arovella Therapeutics has achieved a significant breakthrough in cancer immunotherapy development, with its proprietary CLDN18.2 chimeric antigen receptor (CAR) demonstrating potent activity against pancreatic cancer cells in preclinical testing. The findings represent a crucial advancement in targeting one of medicine's most challenging malignancies.
Proof-of-Concept Study Results
The proof-of-concept study, conducted at the University of North Carolina under Professor Gianpietro Dotti, showed that CAR-T cells engineered with Arovella's patent-protected CLDN18.2 sequence successfully eliminated CLDN18.2-positive pancreatic adenocarcinoma cells. The company's CAR performed on par with CARsgen Therapeutics' leading CLDN18.2 construct, which is currently under regulatory review in China.
"Seeing the robust activity of our novel and proprietary CLDN18.2-targeting CAR against pancreatic cancer cells has the team excited as we expand our pipeline to target difficult-to-treat solid tumours," said Dr Michael Baker, Arovella's CEO and managing director. "It is encouraging that the cytotoxic potential shown in this study was equivalent to a CAR that has an NDA submitted for regulatory approval."
Strategic Advantage Through iNKT Platform Integration
Arovella plans to integrate its CLDN18.2 CAR into its invariant natural killer T (iNKT) cell platform, potentially providing a strategic advantage over conventional CAR-T cell therapies. Unlike traditional CAR-T cells, iNKT cells can reshape the tumor microenvironment and activate additional cancer-killing immune cells.
Recent studies suggest CAR-iNKT therapies may outperform CAR-T cells in treating solid tumors, positioning Arovella's approach as potentially superior for addressing pancreatic and gastric cancers. The company anticipates that the anti-tumor activity of its CAR will be even more effective in vivo when integrated into the iNKT cell platform.
Development Timeline and Next Steps
The company's immediate next steps include engineering iNKT cells to express the CLDN18.2 CAR, followed by evaluation of their activity against tumor models. Arovella will then progress into animal studies focusing on pancreatic and gastric cancer to generate the safety and efficacy data required for human trials.
Market Position in Emerging Field
Arovella is positioning itself as one of only a handful of companies pursuing CLDN18.2 CAR-iNKT therapies, placing it at the forefront of a rapidly evolving field. The approach could potentially redefine treatment options for some of the most challenging cancers, particularly given that pancreatic cancer remains one of the deadliest malignancies with limited treatment options and very low survival rates.
