Navigating CAR-T translation in Australia: lessons from an academic program.

Adoptive cell therapies utilizing both gene-modified and unmodified immune cells have revolutionized treatments for cancer and infection. Seven Chimeric antigen receptor (CAR) T cell products have been approved as therapies, providing the momentum to expand their clinical benefit to several cancer types. Many novel receptor-expressing cell therapies remain in preclinical development and require robust clinical testing Translating these into early-phase clinical trials requires navigating manufacturing, quality, and regulatory systems that are often not documented explicitly for academic investigators. This manuscript provides a stage-by-stage roadmap for translating academic CAR T-cell research into an investigator-led Phase I clinical trial in the Australian public sector. It draws on the E2CAR program, the first clinical translation of an EphA2-directed CAR T-cell product into pediatric bone sarcoma, conducted at the Children's Hospital at Westmead. We present our experience across six stages: construct finalization and vector strategy, manufacturing process development, quality infrastructure, assay development and validation, multi-entity operational coordination, and CTA regulatory engagement and provide recommendations for researchers at each stage. We also present a consolidated program timeline, minimum personnel requirements, and indicative costs to support grant applications and institutional planning. While the operational framework described here was developed specifically for our Health Precinct some of the recommendations we provide are likely to benefit academic groups navigating constraints in comparable settings.