A roadmap for establishing institutional readiness for cellular therapies targeting solid tumours and autoimmune diseases.

Introduction

Adoptive cellular therapies (ACTs) involve the ex vivo expansion of autologous or allogeneic immune cells, with or without genetic modification, to harness the immune system’s capacity to recognise and eradicate malignant cells or recalibrate immune tolerance in chronic autoimmune disease (AID). They represent a transformative advance in immunotherapy, encompassing strategies including Chimeric Antigen Receptor T cell (CAR-T), T cell receptor (TCR) and Tumour Infiltrating Lymphocyte (TIL) therapies 1 – 3 . By enhancing recognition and specificity, ACTs have demonstrated potential to induce durable clinical responses and, in select cases, advance efforts toward curative therapeutic strategies 4 . The emergence of ACTs has precipitated a paradigm shift, accelerating development and clinical trials investigating novel targets and next-generation cellular constructs.

CAR-T therapies targeting CD19 and B cell maturation antigen (BCMA) have transformed the management of haematological malignancies (HM), including B-cell acute lymphoblastic leukaemia (B-ALL), B-cell lymphoma and multiple myeloma (MM), with seven agents now approved by the U.S. Food and Drug Administration (FDA) 1 , 5 . These agents have resulted in high response rates and durable remissions in relapsed/refractory disease after a single infusion 6 , 7 . This clinical success has catalysed rapid efforts to expand ACT to solid tumours and AID, driving the need for institutions to develop the infrastructure and systems required to deliver these complex therapies 4 , 5 , 8 .

Despite the remarkable efficacy of CAR-T therapies in haematological malignancies, translation to other disease settings has followed distinct trajectories. In solid tumours, comparable outcomes have not yet been consistently achieved, and no therapy has, to date, received FDA approval. In this context, next-generation CAR-T constructs engineered to overcome biological and logistical challenges form the basis of an expanding portfolio of early phase clinical trials. As of July 2025, more than 1900 active oncology cell therapy trials were ongoing globally, with over half targeting solid tumours 9 . In solid tumours, CAR-T therapies typically target tumour-associated antigens, with the most commonly investigated including mesothelin (MSLN), Glypican-3 (GPC-3), B7-H3, Claudin 6/18.2, human epidermal growth factor receptor 2 (HER-2), CD70, prostate specific membrane antigen (PSMA), carcinoembryonic antigen (CEA) and epidermal growth factor variant III (EGFRvIII) 10 , 11 .

In contrast, ACTs are increasingly demonstrating encouraging efficacy in chronic AID. The strongest evidence to date has emerged from CD19-directed CAR-T therapy, where profound and sustained immune resetting has been observed in early clinical studies 12 – 14 . CD19-positive B cells and plasma cells represent a key immune reservoir driving disease persistence in autoantibody driven AID, making them an attractive therapeutic target 15 . As of January 2025, 238 cell therapy trials in AID were registered globally, representing a significant increase over the past decade 16 . Clinical trials in Systemic Lupus Erythematosus (SLE), idiopathic inflammatory myopathies (IIM), Multiple Sclerosis (MS) and systemic sclerosis (SSc) have demonstrated sustained, and in some cases universal, remission lasting up to three years 12 – 14 . Collectively, these findings highlight ACTs as a potentially transformative modality to reset immune tolerance and redefine the therapeutic landscape of chronic autoimmunity.

These highlighted advances have catalysed a global surge in clinical trial activity, with numerous studies now exploring novel targets, optimised manufacturing processes, and engineered cellular platforms designed to broaden accessibility and improve long-term outcomes. Between April 2021 and April 2022, active cell therapy trials worldwide increased by 36%, largely driven by CAR-T therapies 17 . As of April 2022, 94% of CAR-T trials were concentrated predominately in China (58.5%) and the United States (34.7%) 18 . Within each country, trial activity was regionally clustered – on the east and west coast of the United States and in the eastern provinces of China. Figure 1 illustrates these global and regional disparities in solid tumour CAR-T trials as of August 2025 19 . Despite the rapid expansion of clinical trials, the real-world implementation of cellular therapies struggles to keep pace. Fig. 1 Global distribution of active and completed CAR-T clinical trials in solid tumours (August 2025). Data were extracted from ClinicalTrials.gov using the search terms “CAR-T” and “solid tumours”, identifying 272 studies registered as active or completed. Of these, 78 (29%) trials were based in the United States ( a ), 178 (65%) in China ( b ) and comparatively few across Europe and the Asia–Pacific region, and minimal representation in low- and middle-income countries. Within the United States, trials were predominantly clustered on the east and west coasts, while in China activity was concentrated in eastern provinces. This geographic concentration underscores the global imbalance in trial activity and highlights the need for broader international collaboration to ensure equitable evaluation and delivery of CAR-T therapies. Figure created by the authors using Datawrapper (Datawrapper GmbH, Berlin, Germany).

Broader adoption of cellular therapies is constrained by biological and operational factors. Biological factors such as tumour heterogeneity, limited antigen specificity, and immunosuppressive tumour microenvironments continue to limit efficacy in solid tumour ACT. Concurrently, operational and logistical constraints (Fig. 2 ), including complex manufacturing processes, high costs, prolonged vein-to-vein timelines, and specialised infrastructure requirements, pose significant barriers to scalability and equitable access. Although several regulatory and policy initiatives have been introduced to accelerate dissemination of ACT, such as expediated approval pathways in the United States and China, and locally manufactured academic CAR-T programs in countries including Spain, Brazil, and Israel that substantially reduce per-dose costs, availability and accessibility remain highly heterogenous across regions 1 , 20 . Fig. 2 Key operational and logistical barriers limiting implementation of solid organ CAR-T therapies. Schematic representation of major barriers to CAR-T delivery. Logistical challenges encompass cryogenic transport and storage, synchronisation of dosing with manufacturing timelines, and reliable communication between centres. Operational challenges include the labour-intensive nature of autologous manufacturing, limited capacity, and need for specialised infrastructure. Socioeconomic barriers are driven by high costs and inequitable access for patients in resource-limited or geographically remote settings. Regulatory challenges reflect heterogeneous frameworks, variable approval pathways, and quality assurance requirements across different regions.

While ongoing innovation in next-generation constructs, manufacturing platforms, and regulatory frameworks may address scalability over time, this article focuses on the practical strategies and institutional considerations required to safely deliver CAR-T therapies in real-world clinical settings. Institutional ‘readiness’, which encompasses the clinical, operational and logistical capacity to safely deliver complex cellular therapies, has emerged as a critical determinant of successful implementation. Furthermore, published guidance on how centres establish and operationalise readiness frameworks remains limited.

This article outlines a pragmatic blueprint for institutional readiness, grounded in the experience of St Vincent’s Hospital Sydney, one of the first Australian centres to deliver CAR-T therapy for solid tumour and AID. We incorporate cross-institutional insights from the Peter MacCallum Cancer Centre and highlight shared lessons applicable across diverse health systems. By sharing this institutional roadmap, we aim to facilitate effective capacity building across a variety of clinical settings and to accelerate the safe, sustainable and equitable global adoption of cellular therapies.

Establishing institutional readiness for adoptive cellular therapies: six domain roadmap

The delivery of cellular therapies in real-world settings is inherently complex and resource-intensive, requiring meticulous planning and coordinated multidisciplinary collaboration to ensure safe, effective and sustainable implementation. Institutional readiness extends beyond clinical expertise alone and demands structured organisational planning across multiple operational domains.

In 2023, the St Vincent’s Early Phase Clinical Trials Unit was competitively selected to participate in a first-in-human CAR-T trial in colorectal carcinoma, alongside CAR-T clinical trials in multiple sclerosis and systemic sclerosis. Importantly, our institution has a 50-year history of haematopoietic stem cell transplantation for malignant and non-malignant disorders including AID, and more recently, CAR-T therapies for haematological malignancies as standard of care or in a clinical trial setting, providing established infrastructure, governance processes, and an experienced multidisciplinary workforce. Existing haematology-led systems for patient prioritising or scheduling, apheresis and cell collection, dedication inpatient beds and expertise in toxicity management were leveraged to support expansion to solid tumours and AID. Rather than creating a separate service, solid tumour and AID CAR-T trials were embedded into this existing framework. Disease specific specialists retain responsibility for primary disease and trial oversight, partnering closely with the haematology team for collection logistics, admission planning and toxicity management. We recommended that this integrated model be utilised for any centre hoping to develop similar programs, rather than building stand-alone pathways.

From our experience, we have identified six interdependent domains essential to successful program implementation, highlighted in Fig. 3 ; 1) education and shared learning, 2) multidisciplinary collaboration, 3) specialised infrastructure and resources, 4) proactive toxicity management and monitoring, 5) patient triage and waitlist coordination, and 6) patient and caregiver education and support. These domains form a pragmatic roadmap to guide centres seeking to establish or expand cellular therapies. Fig. 3 Blueprint for institutional readiness for adoptive cellular therapies, outlining a framework across six essential domains. (1) multidisciplinary collaboration, (2) education and shared learning, (3) specialised infrastructure and resources, (4) patient triage and waitlist coordination, (5) patient and caregiver education and support, (6) proactive toxicity monitoring and management. These domains collectively provide the foundation for safe, efficient, and scalable implementation of cellular therapies.

Education and shared learning

Successful implementation of ACT beyond haematological malignancies requires clinicians, nursing staff, and allied health professionals, many of whom have limited prior experience with cellular therapies, to rapidly develop familiarity with novel workflows, unique toxicity profiles, and monitoring requirements to ensure patient safety. Deliberate investment in education and shared learning was therefore foundational to institutional readiness.

Prior to trial initiation, investigators from the Early Phase Oncology unit at St Vincent’s Hospital undertook a site visit and knowledge-sharing session with colleagues at the Peter MacCallum Cancer Centre in Victoria, one of the few Australian centres with prior experience in solid tumour CAR-T trials. Knowledge gained into their standard operating procedures (SOPs), implementation strategies, and approaches to toxicity management provided an invaluable foundation for local protocol development and institutional preparedness.

Building on this foundational knowledge, our team collaborated with haematology, pharmacy, nursing, intensive care, neurology, and emergency medicine, to develop trial- and institution-specific guidelines. These were subsequently incorporated into existing joint accreditation committee of international society for cellular therapy and European Group for blood and marrow transplantation (JACIE) -accredited SOPs through the haematology department, ensuring consistency, governance and sustainability of practice.

To support hospital-wide readiness, a cross-departmental educational program was delivered across oncology, haematology, relevant inpatient wards, intensive care, the infusion centre, and the emergency department. Educational sessions emphasised the unique challenges of CAR-T in solid tumours and autoimmune disease, reinforced principles of early recognition and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and outlined escalation pathways and treatment algorithms. This structured and proactive educational approach strengthened staff confidence, optimised patient safety, and facilitated the integration of cellular therapies into routine hospital workflows.

Multidisciplinary collaboration

The delivery of ACT across solid tumours and AID spans multiple specialities, care settings, and phases of treatment, creating significant coordination challenges that can compromise safety, efficiency, and timely access to care. Successful implementation of complex cellular therapies necessitates coordinated multidisciplinary collaboration spanning the entire patient journey, from referral and treatment planning through to post-infusion monitoring and toxicity management (Fig. 4 ). At our institution, a robust collaborative framework was established prior to enrolment of the first patient in each field. Early engagement of disease-specific national consumer organisations was essential to optimise awareness of these studies across all eligible Australian patients and ensure equity of access. Referrals for non-malignant indications were typically received by the relevant specialist (eg: SLE indication referred to Rheumatologist, MS indication to Neurologist) and screened for suitability. The haematology teams, with their extensive expertise in haematological CAR-T therapies, were integral during the foundational phase, guiding protocol development, informing site-specific lymphodepletion regimens, infusion pathways, and toxicity monitoring, facilitating the adaption of workflows to both the solid tumour and AID context. To ensure appropriateness, cases were discussed at both national disease-specific expert MDTs then subsequently at weekly institutional ACT meetings. Early engagement with pharmacy ensured the preparation of lymphodepleting chemotherapy, antimicrobial prophylaxis, and supportive medications, while coordination with the apheresis unit facilitated timely scheduling and cell collection for manufacturing. Fig. 4 Patient journey for adoptive cellular therapies, divided into four phases. (1) Referral and eligibility, (2) Pre-treatment work-up, including baseline multidisciplinary assessments and patient education, (3) Treatment, encompassing apheresis, lymphodepleting chemotherapy, and cell therapy infusion, and (4) Monitoring and follow-up, including acute inpatient observation and long-term outpatient assessment of treatment efficacy and adverse effects.

Operational alignment was coordinated through weekly multidisciplinary meetings to synchronise scheduling and capacity alongside standard-of-care haematology patients. Baseline neurological assessments, including MRI brain and EEG, together with neurology review, facilitated pathways for rapid evaluation and intervention in the event of neurotoxicity. Patients were synchronously reviewed by oncology (solid tumours), rheumatology (SSc) and haematology (all) prior to dosing, with anti-seizure prophylaxis considered in high risk individuals. Conjoint admissions within the haematology ward during dosing and early monitoring leveraged the expertise of nursing, medical and allied health staff in managing complex toxicites. Ongoing communication with referring physicians facilitated timely patient identification, bridging therapy planning, and scheduling of washout periods prior to lymphodepletion and CAR-T infusion.

Clinical trial nursing coordinators provided the operational backbone of these trials, with key responsibilities in patient education, logistics, toxicity monitoring and protocol adherence. This structured multidisciplinary framework was fundamental to institutional readiness and the safe delivery of CAR-T therapies in solid tumours and autoimmune disease.

Specialised infrastructure and resources

The safe and effective delivery of CAR-T therapies requires specialised infrastructure, dedicated resources, and trained personnel, as delays in cell handling or escalation of care can compromise safety and treatment integrity. Beyond physical infrastructure, logistical complexity across the vein-to-vein pathway; including cell collection, cryopreservation and transport, alignment of dosing with manufacturing timelines, and communication between collection, manufacturing, and treatment centres, creates significant barriers to timely treatment, equitable access and scalability.

At our institution, dedicated treatment areas equipped with apheresis and cell processing capacity, including cryopreservation, were staffed by trained professionals experienced in collection, processing and infusion. Therapy initiation was carefully coordinated with manufacturing schedules through weekly operational meetings allowing early identification of capacity constraints and proactive patient prioritisation.

Given the risk of acute and unpredictable toxicities, equally critical was the establishment of a robust support system for managing complications, with 24/7 access to emergency care, diagnostic imaging and intensive care facilities to support patients with severe CRS or ICANS requiring inotropes or ventilatory support.

To ensure sustainable capacity, institutional processes for resource planning were embedded through the Research Operations Assessment Committee (ROAC). This committee, comprising executive officers, the head of research operations and clinical trials quality manager, was established to evaluate the operational, staffing and resource impacts of proposed clinical trials. The ROAC committee focuses on operational feasibility for research studies involving planned inpatient admissions, those at high risk of unplanned admissions or studies requiring expanded support from services such as nursing, pharmacy, pathology or allied health. Core functions are centred around assessing 1) the inpatient and outpatient impact, 2) financial impact, 3) staffing impact, 4) pharmacy impact, 5) site and facility readiness and, 6) risk management. By balancing the demands of early-phase trials against standard-of-care services, this structured oversight ensures sustainable delivery of complex cellular therapies while safeguarding hospital resources.

Recognising that many institutions may not have access to the infrastructure or resources of large tertiary referral centres, we have developed a pragmatic, tiered readiness framework to improve the applicability of this roadmap across diverse healthcare settings (Table 1 ). We propose a three-tier model to reflect varying institutional capabilities and promote equitable access to cellular therapies. This structure allows progressive capacity building and collaboration across health systems while maintaining patient safety. Table 1 Tiered Institutional Readiness Model for Cellular Therapy Delivery Tier Role in network Typical setting Scope of activity Core capabilities Tier 1 – Foundational/referral Identify, counsel, stabilise and refer patients Community or regional centres Screening, shared care, follow-up, long term care Basic clinician education, referral pathways, toxicity recognition, access to urgent transfer, shared-care protocols Tier 2 – Delivery-capable Administer Licensed products Large regional or metropolitan centres Commercial ACT infusion and monitoring Trained multidisciplinary team, SOPs for product handling, inpatient beds, CRS/ICANS management protocols, ICU access, pharmacy access Tier 3 – Comprehensive/academic hub Conduct clinical trials with novel constructs Tertiary or academic centres Complex/high-risk cases, early-phase trials, program development Dedicated ACT unit, onsite apheresis, clinical trials unit, regulatory team, research capability, accreditation (FACT/JACIE), advanced subspeciality support Tier 1 centres function as referral or shared-care sites, focusing on patient identification, education, and toxicity recognition. Tier 2 centres are delivery-capable institutions able to safely administer licensed products with appropriate monitoring and governance. Tier 3 centres serve as comprehensive hubs with advanced infrastructure, accreditation, and clinical trial capability, supporting innovation and regional networks.

Proactive toxicity management and monitoring

Life-threatening toxicities, particularly Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity (ICANS), remain a significant limitation of CAR-T therapy 21 , 22 . These toxicities are primarily mediated by monocyte and macrophage activation, resulting in downstream release of IL-6 and IL-1 21 . CRS typically occurs within hours to a week post-infusion, correlating with exponential CAR-T cell expansion, and it manifests as systemic inflammation, capillary leak, coagulopathy, and potential multi-organ dysfunction 22 . Although CRS can be severe, it is generally reversible with prompt supportive care. Tocilizumab, an IL-6 receptor antagonist, is standard first-line therapy for Grade ≥2 CRS, with corticosteroids or anakinra (an IL-1 receptor antagonist) reserved for refractory cases 21 , 23 . ICANS typically arises one to three weeks post-infusion, presenting as confusion, agitation, seizures, delirium, encephalopathy, or cerebral oedema 21 , 22 . The pathophysiology of ICANS is less well defined but is thought to involve accumulation of inflammatory cells and cytokines within the cerebrospinal fluid and brain parenchyma 22 .

In solid organ malignancies, CRS incidence varies widely (any-grade 37–93%; ≥Grade 3, 1–23%), influenced by disease burden, CAR-T dose, lymphodepleting chemotherapy regime, and construct design 24 , 25 . In AID, CRS and ICANS have been far less common to date, likely due to the comparatively lower cellular burden, however wider application to neuroimmunological disorders with impaired blood-brain barrier will require heightened vigilance 26 .

Novel toxicities are increasingly recognised, including macrophage-activation syndrome with haemophagocytic lymphohistiocytosis (HLH)-like phenotype 25 , immune effector cell colitis, BCMA CAR-T–associated Parkinsonism, cranial nerve palsies, Guillain barre like syndromes 27 , GPRC5D CAR-T–associated cerebellar toxicity, and the recently defined Local Immune Effector Cell–Associated Toxicity Syndrome (LICATS) 28 . The expanding spectrum and severity of recognised toxicities may limit the future application of ACT in conditions that cause morbidity without substantially impacting mortality.

Institutional readiness for the potential life-threatening toxicities of CAR-T therapy requires comprehensive planning, subspecialist input and robust monitoring pathways to ensure prompt and expedient intervention for toxicities. At our site, a hospital wide protocol for recognition and management of CRS and ICANS was developed and approved by the Drugs and Therapeutics Committee in November 2024. All patients receiving their first cycle of CAR-T therapy are admitted for close inpatient monitoring, facilitating rapid intervention if toxicities develop. Rescue medications are prepared in advance by pharmacy under established protocols, and treating investigators remain immediately contactable at the bedside. Serious adverse events within the research setting are reported within 24 hours of investigator awareness, ensuring timely escalation and regulatory compliance.

As an additional safeguard, patients are required to remain within a specified radius of the hospital during the first month post-infusion and are required to have a reliable carer present 24/7. Education at discharge, delivered to patients and their carers, reinforce early recognition of warning symptoms, and direct emergency contact pathways are provided to ensure rapid access to the clinical team. As the number of patients receiving cellular therapies continues to grow, attention needs to shift toward long-term post-treatment care. These patients often experience prolonged cytopenias, hypogammaglobulinaemia, and persistent immunosuppression, necessitating structured approaches to infection prophylaxis, revaccination, and monitoring for late toxicities such as B-cell aplasia or secondary malignancies. These considerations highlight the importance of multidisciplinary collaboration and the development of institutional guidance, particularly for teams less familiar with managing cellular therapy–related complications, to ensure safe and coordinated long-term care for this emerging patient population.

Overall, effective toxicity management requires vigilant monitoring, comprehensive mitigation strategies and timely intervention, imposing significant resource and operational demands.

Patient triage and waitlist coordination

Given the labour-intensive and time-consuming nature of autologous CAR-T manufacturing, delays remain a significant risk, with vein-to-vein times ranging from 18 days to 2–3 months 29 . In one study, up to 25% of patients with relapsed/refractory multiple myeloma died or required hospitalisation due to disease progression while awaiting therapy 29 . Capacity constraints at both manufacturing and treatment centres exacerbate these challenges, highlighting the need for ethical frameworks to prioritise patients based on disease burden, urgency, likelihood of manufacturing success, psychosocial readiness, and toxicity risk. Prolonged manufacturing timelines and limited treatment capacity, leading to potential delays between referral and infusion, can compromise patient eligibility, as disease progression or clinical deterioration may render patients unfit for treatment. Inequities also arise early in the care pathway, with delayed or absent referral from non-CAR-T centres representing a major barrier to equitable access. Limited awareness of trial availability, eligibility criteria and referral pathways can result in missed opportunities for patients.

Treatment delays occur at two critical stages: brain-to-vein time (from referral to leukapheresis) and vein-to-vein time (from apheresis to infusion of cells), both of which significantly influence patient outcomes. A recent multicentre retrospective analysis comparing patients with relapsed or refractory large B-cell lymphoma treated with CAR-T therapy in the United States versus Europe demonstrated markedly longer referral to infusion intervals in Europe (median 66 days vs 50 days), associated with inferior progression-free survival (3.1 months vs 9.2 months) 30 . These findings underscore the clinical impact of manufacturing and logistical delays on treatment outcomes.

At our site, early referral and structured triage were prioritised to mitigate these risks. Patient selection considered both disease-related factors (e.g. disease burden, progression rate) and patient-related factors (e.g. fitness, comorbidities, social support). Bridging therapy, recommended to maintain disease control and minimise tumour burden, requires careful coordination with treatment wash out requirements prior to cell infusion. Emerging innovations such as accelerated manufacturing, decoupled administration, and “off-the-shelf” products hold promise to further reduce manufacturing delays and improve equitable access 31 .

This proactive approach to referral networks, triage, and waitlist management maximises the likelihood that patients remain eligible, proceed to infusion of an in-specification product, experience less toxicity, and achieve favourable outcomes.

Patient and caregiver education and support

Complex treatment pathways, prolonged manufacturing timelines, risk of unpredictable toxicities, and the substantial psychosocial burden associated with cellular therapy can compromise adherence, delay escalation of care, and ultimately affect patient safety and equitable access. Accordingly, comprehensive patient and caregiver education is embedded from the outset to support informed consent, realistic expectations, and safe participation throughout the treatment journey.

Patients are counselled and educated on expected treatment timelines, including manufacturing lead time, hospital admission requirements, monitoring schedules, and the potential for acute and delayed toxicites. Standardised educational materials are provided to reinforce verbal counselling. For example, the Peter MacCallum Cancer Centre’s guide on CAR-T therapy for patients, carers, and families, which outlines the treatment process, eligibility criteria, and available support services, illustrating the value of clear, consistent information delivery 32 .

Patient access can be further restricted by the uneven geographical distribution of treatment facilities, disproportionately disadvantaging those in regional or resource-limited settings. To address this, social work engagement occurs early to address accommodation, financial and psychosocial needs, thereby reducing logistical barriers.

Given the risk of acute complications, such as CRS and ICANS, patients are required to have a dependable caregiver available 24 hours a day during the high-risk post-infusion period to facilitate early symptom recognition and facilitate rapid access to care. All patients and caregivers are provided with direct 24/7 contact details for the treating clinical team, ensuring timely communication, fostering trust, and ensuring rapid escalation of care should complications arise.

Collectively these measures operationalise a patient-centered model of care which integrates education, psychosocial support and clear communication as fundamental to the safe delivery of ACT. The practical impact of these measures on patient experience is illustrated in Box 1 , which provides a first-hand narrative from a patient treated at St Vincents Hospital Sydney, reflecting on the value of coordinated multidisciplinary care, safety education and communication throughout the process.

“Having access to participate in the trial within my usual treatment centre was a key factor in my positive experience. Being treated in a familiar environment, surrounded by a team I already trusted, minimised disruption to my daily life and reduced anxiety during a complex treatment process. The proactive and collaborative approach of my oncologist and trials team also made a significant difference. Early discussions about the trial alongside my existing care allowed a seamless transition without compromising my ongoing treatment. Clear, consistent communication and close coordination between multiple team members helped me feel informed and supported throughout dosing and monitoring.”

Operational implications: Deliver therapy within familiar local centres where feasible Integrate trial discussions early within standard care planning Provide dedicated coordination across oncology, trials, and nursing teams Ensure clear, consistent patient education and communication Foster multidisciplinary collaboration to minimise logistical and psychosocial burden

Conclusions and Future Directions

The remarkable success of cellular therapies in HM has invigorated efforts to expand these approaches to solid tumours and AID. Recognition of the biological barriers constraining efficacy in these settings has precipitated rapid expansion of clinical trial activity exploring novel targets, optimised manufacturing processes and engineered cellular platforms. Despite these advances, real-world implementation remains concentrated in major metropolitan centres, with China and the United States leading activity. Widespread integration of cellular therapies into routine practice will require robust operational, logistical and governance frameworks. Current processes contribute to delayed referral, prolonged manufacturing timelines, imbalances between supply and demand, financial toxicity, and limited global accessibility. As the promise and demand for ACTs grow, optimising manufacturing workflows to enable scalability will be critical.

Effective adoption of cellular therapies in solid tumours and autoimmune disease requires deliberate, stepwise institutional development. This encompasses infrastructure, fostering multidisciplinary collaboration, workforce expansion and training, and the implementation of robust operational protocols. The substantial time, resources, and iterative experience required underscore the value of structured planning and early engagement with established centres of expertise. By outlining our experience in establishing solid tumour and autoimmune CAR-T trials at St Vincents Hospital in Sydney, we aim to provide a practical framework that may facilitate expansion of access to other centres wishing to embark on similar initiatives.

Evolving trends demonstrate a marked shift toward pre-commercial biopharmaceutical companies as the primary drivers of cell therapy clinical trial expansion, accounting for 82% of all cell and gene therapy trials conducted between 2020 and 2024 33 . These emerging companies, often operating with fewer resources, increasingly rely on clinical research organisations (CROs) for expertise, infrastructure and scalable support. However, CROs may have limited familiarity with the unique complexities of cell therapy development and toxicity management, shifting the burden of clinical oversight to trial sites. Further, as capacity a major referral centres becomes saturated, pressures arise to dose patients at less experienced centres. In this evolving environment, coordinated safety and monitoring committees, oversight from experienced centres, and national consortia or networks will be essential to ensure that the continued expansion of cell-therapy trials and real-world implementation remain safe and patient-centric.

Alongside commercial and pre-commercial programs, several low- to middle-income countries have pioneered publicly funded, academic-led CAR-T programs to improve affordability and access. Notable examples include the Spanish ARI-0001 program developed at Hospital Clínic de Barcelona 34 , the Brazilian initiative in collaboration with the not-for-profit US-based Caring Cross 20 , and Israel’s academic CAR-T program at Hadassah Medical Center. These non-commercial models demonstrate the feasibility of in-house manufacturing at a fraction of the cost of commercial products, highlighting a viable pathway for sustained expansion.

National consortia, such as the French UNITC 35 , the Australian National Immune Effector Cell Patient Prioritisation Committee and the CAR-T toxicities consortium of the American Society of Haematology 36 , have been established to coordinate collaborative efforts, streamline manufacturing and quality-control procedures, and enable collective learning from real-world patient outcomes while overcoming regulatory and access barriers 37 . Expanding such initiatives with global reach to standardise procedures would further enhance equity and extend access.

Future efforts must prioritise scalable, sustainable, and patient-centered models of care. Key strategies include investment in decentralised or point-of-care manufacturing, digital platforms for real-time coordination between collection and treatment sites, and integrated referral networks to reduce geographic inequities. Emerging innovations, such as in vivo cellular therapy platforms (e.g. in vivo gene delivery using nanoparticles and viral vectors) and “off-the-shelf” allogeneic constructs, offer the potential to simplify manufacturing, reduce treatment delays, and broaden patient access 38 . Complementary technological advances, including artificial intelligence-assisted patient triage, decision support, and predictive toxicity modelling, may further enhance patient selection, toxicity management, and personalised treatment pathways 39 . In parallel, international harmonisation of regulatory standards, accreditation frameworks, and formalised training programs will be essential to ensure consistency, safety, and equity of delivery worldwide. Recent efforts, including the FACT Standards for Immune Effector Cells in the Community Clinical Setting, 1st edition, extend consensus-based quality and safety guidance to community oncology programs delivering CAR-T and other immune effector therapies, supporting delivery closer to patients’ homes 40 .

Looking ahead, overcoming logistical and operational challenges will be as pivotal as scientific breakthroughs in shaping the future of ACTs. Addressing these operational barriers will accelerate trial activation and delivery, expand patient access across diverse health systems, and help realise the transformative potential of cellular therapies beyond haematology.

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Acknowledgements

There are no acknowledgements to be made for this manuscript. No funding was received for the preparation of this manuscript.

Author contributions

S.C., J.M., and J.L. conceptualised and organised the manuscript structure, content, and figures. S.C., D.M., E.H., R.C., J.M., V.C., V.V., A.O.G., S.K.J., A.M., S.G., H.T., B.W., C.N., A.H., P.P., J.B., D.F., A.R., G.S., K.I., C.M., B.K., N.D.L., H.B., P.C., A.J., L.G., B.T., J.D., S.J.H., J.M., and J.L. contributed to drafting and critical revision of the manuscript and approved the final version for submission. All authors agree to be accountable for all aspects of the work.

Data availability

No datasets were generated or analysed during the current study.

Competing interests

Several authors are investigators on cellular therapy clinical trials and receive institutional funding to support the conduct of these trials. These funds are provided to their institutions and not directly to the authors. No personal financial interests are declared in relation to the subject matter of this study.

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