An Australian Narrative Review of Adoptive Cellular Therapies in Malignancy: Expanding Indications, Referral Pathways and Safety Beyond Specialist Centres

Adoptive cellular therapies (ACT), including tumour-infiltrating lymphocyte (TIL), T-cell receptor-engineered T (TCR-T) cell and chimeric antigen receptor T-cell (CAR-T) therapies, represent an evolving class of immunotherapies with established efficacy in selected haematological malignancies and emerging applications in solid tumours. Additional platforms under investigation include virus-specific T cells, tumour-associated antigen-specific T cells, natural killer (NK) cell therapies and dendritic cell-based therapies. The therapeutic scope of ACT is expanding beyond oncology into autoimmune and fibrotic diseases, infectious diseases and inherited metabolic and immune disorders, highlighting the broad potential of cellular immunotherapy platforms. In solid tumours, efficacy remains limited by tumour antigen heterogeneity, immunosuppressive tumour micro-environment and impaired immune cell trafficking and persistence. These barriers are driving development of next-generation cellular products and combination strategies. Characteristic immune-mediated toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain important considerations. Although potentially severe, these toxicities are generally manageable with early recognition, multidisciplinary care and prompt specialist intervention. As ACT indications expand in Australia, clinician familiarity with indications, mechanisms of action and toxicity profiles is essential to support informed patient discussions, appropriate patient selection, timely referral and prompt toxicity recognition and management. Non-oncology specialists have an important role in shared care, including patient identification, referral coordination, monitoring for delayed or late toxicities and provision of ongoing survivorship and supportive care. Achieving equitable national access to ACT will require streamlined health technology assessment processes, coordinated reimbursement and delivery funding models and structured referral networks with cross-institutional collaboration to support the specialised infrastructure required for their delivery.