How Arovella’s CLDN18.2 CAR-T Cells Could Transform Pancreatic Cancer Treatment

• Novel CLDN18.2 CAR-T cells kill pancreatic cancer cells in vitro
• Performance comparable to competitor’s CAR-T therapy under regulatory review in China
• Plans to incorporate CAR into iNKT cells for enhanced solid tumour targeting
• Upcoming in vivo studies in pancreatic and gastric cancer mouse models
• Arovella among few developing CLDN18.2-targeting CAR-iNKT therapies

A Promising Step Against Pancreatic Cancer

Arovella Therapeutics Ltd (ASX – ALA) has announced a significant milestone in its cancer immunotherapy pipeline with the successful demonstration that its proprietary CLDN18.2-targeting CAR-T cells can robustly kill pancreatic cancer cells in vitro. This proof-of-concept study, conducted at the University of North Carolina under Professor Gianpietro Dotti, used a pancreatic adenocarcinoma cell line naturally expressing CLDN18.2, a protein increasingly recognised as a valuable target in solid tumours.

Pancreatic cancer remains one of the most aggressive and difficult-to-treat cancers, with limited effective therapies and poor survival rates. Arovella’s ability to induce potent cytotoxicity against these cells marks a promising advance in addressing this unmet medical need.

Matching a Leading Competitor

The company’s CLDN18.2 CAR design is based on patent-protected antigen-binding sequences licensed exclusively from Sparx Group, derived from the SPX-101 monoclonal antibody. In comparative assays, Arovella’s CAR-T cells performed equivalently to a CAR developed by CARsgen Therapeutics, whose product CT041 has recently had its New Drug Application accepted for review by China’s National Medical Products Administration. This parallel underscores the robustness of Arovella’s CAR construct and validates its potential clinical relevance.

Advancing to CAR-iNKT Cell Therapy

While CAR-T therapies have shown promise, Arovella is focusing on its innovative CAR-iNKT cell platform. iNKT cells, a unique subset of immune cells, have demonstrated superior ability to modulate the tumour microenvironment and activate other immune cells, potentially overcoming the challenges faced by CAR-T cells in solid tumours. The company plans to incorporate its CLDN18.2 CAR into iNKT cells and proceed with in vivo studies in mouse models of pancreatic and gastric cancer.

This approach could offer a more effective and durable treatment option for patients with these difficult cancers, positioning Arovella among a select group of companies pioneering CLDN18.2-targeting CAR-iNKT therapies.

Looking Ahead

CEO Dr Michael Baker expressed optimism about the results, highlighting the equivalence to a CAR-T product already under regulatory review and the potential for enhanced efficacy through the iNKT platform. The next critical steps will involve demonstrating safety and efficacy in animal models and generating the necessary data to support human clinical trials.

As Arovella advances this program, the broader oncology and investor communities will be watching closely to see if this novel immunotherapy can translate its promising preclinical activity into meaningful clinical outcomes.

Bottom Line?

Arovella’s next moves in CAR-iNKT development could redefine solid tumour immunotherapy if preclinical promise holds true.

Questions in the middle?

• Will Arovella’s CLDN18.2 CAR-iNKT cells demonstrate superior efficacy in vivo compared to CAR-T cells?
• What is the anticipated timeline for IND-enabling studies and first-in-human trials?
• How will Arovella’s therapy differentiate itself in the competitive CLDN18.2-targeting immunotherapy landscape?