Cell and gene therapy (CGT) has revolutionized medicine, tracing its origins to hematopoietic stem cell transplantation, a cornerstone for treating cancers and genetic diseases. This foundation paved the way for countless clinical trials for other forms of cellular-based therapies in oncology, resulting in the first genetically modified cell therapy, a CAR T-cell therapy approved by the FDA in 2017. Since then, 10 additional CAR T therapies have reached commercialization to treat blood cancers. Today, more than 34,000 patients worldwide have received CAR T therapy.
Expanding CAR T indications: learnings from oncology
This regulatory and commercial success has led researchers and drug developers to explore new opportunities for cell therapies. While CAR Ts to date have been synonymous with oncology, the potential of cell therapies to address non-oncological diseases is now emerging as the next frontier in CGT innovation.
The application of CAR T has not only successfully addressed otherwise incurable leukemias and other cancers but also provided valuable safety and efficacy insights for patient care. For instance, despite the widespread success of CAR T there have been challenging immunologic side effects, such as cytokine release syndrome and neurotoxicity, which can now be mitigated with immune modulators and anti-inflammatory strategies.
The immunomodulatory potential of CGTs presents a key opportunity in autoimmune disorders, where they can offer a curative solution by eliminating or dampening autoreactive immune cells, specifically targeting B or plasma cells, the source of the pathogenic autoantibodies.
Engineered anti-CD19 and anti-B cell maturation antigen (BCMA) CAR T therapies have shown early clinical success for treating disorders like systemic lupus erythematosus, refractory antisynthetase syndrome and myasthenia gravis, with durability and minimal side effects. There are at least 78 such clinical trials for a broad range of autoimmune disorders, and nearly 100 others utilizing CGTs like mesenchymal stem cell and Treg based therapies, targeting approximately 30 autoimmune diseases. FDA has so far approved three autologous hematopoietic stem cell-based therapies, offering hope to patients with beta-thalassemia and sickle cell disease.
Although clinical trials for non-oncological indications are still rare relative to oncology, promising candidates are emerging — for example, a Parkinson’s disease therapy using dopamine-producing neurons derived from genetically modified pluripotent stem cells, and an allogeneic stem cell-based islet cell therapy for type 1 diabetes. These advancements showcase the growing potential of genetically modified cell-based therapies to address a wider range of diseases.
CGT growing pains
As CAR T therapies move into earlier stages of cancer treatment, more patients can benefit from this groundbreaking approach. At the same time, expanding indications beyond blood cancers means even more people may become eligible for CGT. To meet this rising demand, both production and treatment capacities must scale significantly. However, this growing demand presents challenges for global developers, including high manufacturing costs, regulatory compliance, and the need for scalable production to make these therapies both affordable and accessible.
Regulatory bodies, such as the FDA and EMA, are now better equipped than they were during the first wave of approvals, which bodes well for the coming wave of innovative non-oncological CGTs. Despite this progress, differing frameworks add complexity to an already intricate regulatory landscape that global cell therapy providers must navigate.
However, all these guidelines share a common requirement: adhering to GMP principles and ensuring that every manufacturing step is documented in a traceable manner. To meet this need, the industry is increasingly adopting electronic and automated recording systems. These technologies not only support cGMP-compliant documentation but also help reduce the risk of human error and lower costs by minimizing reliance on skilled operators for manual oversight.
Manufacturing is another major stumbling block. Right now, approved CGTs rely heavily on manual processes that require skilled technicians to oversee every step. These labor-intensive methods are prone to contamination, human error, and inconsistencies — issues that simply won’t scale to meet the growing demand.
Automated manufacturing solutions
The variety of automated platforms now available are allowing cell therapy developers to select technologies that align with their specific manufacturing needs. Modular approaches provide additional flexibility, enabling tailored automation solutions. Unlike all-in-one devices, which remain occupied for the entire manufacturing process — even when certain components are idle — modular systems optimize device utilization, reducing downtime and improving efficiency.
Given the relatively recent growth of CGT clinical trials beyond blood cancers, developers in these spaces are less likely to be burdened with legacy manual manufacturing paradigms. Adopting functionally closed automation systems early, during clinical trial manufacturing, allows for a smoother transition to large-scale commercial production, eliminating the need for process redesigns later.
Automated systems offer several advantages, including minimizing contamination risks, ensuring consistent quality, and reducing the need for expensive cleanroom environments and extensive staff training — all while maintaining high manufacturing standards. Currently, the strict requirements for cleanrooms and highly trained personnel create a significant barrier to expanding beyond a CGT developer’s primary manufacturing facility. These challenges also apply to companies looking to transfer their manufacturing process to a CDMO, establish new centralized manufacturing sites in different regions or even transition to decentralized or point-of-care (PoC) manufacturing models.
Scaling up production capacity is particularly challenging for autologous therapies, where each dose is personalized for an individual patient. These therapies come with exceptionally high costs due to the variability of patient-derived cells and the stringent quality controls required to ensure safety and efficacy. However, the reduced urgency in treating non-oncology indications allows for more flexible scheduling of treatment and manufacturing, potentially lowering overall costs.
The next phase
Manufacturing autologous CGTs for oncologic indications is dictated by the urgency of the disease, making demand highly unpredictable. It is impossible to forecast exactly how many patients will require therapy each week or month, yet these patients cannot afford to wait for a manufacturing slot. In the early days of CGT, reports repeatedly highlighted cases where patients were enrolled in clinical trials, had their cells collected, but unfortunately passed away before manufacturing could begin due to slot unavailability.
To prevent such situations, therapy providers would need to maintain manufacturing capacity at the highest projected demand level. However, this approach is rarely economical, as it would mean running facilities below full capacity most of the time.
In contrast, autoimmune disorders generally progress more slowly than cancer, reducing the urgency of treatment timelines. This allows for greater flexibility in scheduling manufacturing slots, making production planning more predictable. By optimizing and automating manufacturing workflows, CGT manufacturers can better align production with demand, ensuring facilities operate at full capacity.
PoC manufacturing presents a further advantage for the next generation of CGTs by enabling on-demand therapy production while eliminating logistical and time challenges associated with shipping patient cells between collection and manufacturing sites. Automated platforms, with their smaller cleanroom footprint compared to manual processes, are a strong option for space-constrained environments.
By reducing cleanroom space requirements and the need for highly specialized personnel, automated platforms could make PoC manufacturing more viable. Given the predictable scheduling of autoimmune treatments, hospitals could even house automated infrastructure, with a skilled manufacturing operator traveling to oversee key steps — such as manufacturing initiation, genetic modification, and final quality control. This approach would optimize patient experience by shortening vein-to-vein time while maintaining high production efficiency.
A CGT future
Allogeneic therapies are often seen as the future of CGT, offering the potential to make these treatments more affordable and widely accessible. By using universal donor cells, companies can produce “off-the-shelf” treatments at scale, significantly reducing costs. However, challenges such as immune rejection and graft-versus-host disease (GvHD) still need to be addressed. Unlike autologous therapies, which require complex coordination to ship patient-derived cells to and from manufacturing sites under strict time constraints, allogeneic manufacturing eliminates these logistical hurdles. Production batches can be scheduled in advance, tested, and released during standard working hours, rather than operating under the urgent, patient-dependent timelines of autologous therapies.
Additionally, allogeneic manufacturing offers greater predictability as starting material remains consistent — unlike autologous therapies, where variability can lead to poor yields or failed runs. A failed allogeneic batch can be replaced, ensuring reliable supply, while autologous failures may leave patients without treatment. Standardized allogeneic processes also simplify automation, unlike autologous manufacturing, which often requires patient-specific adjustments. This makes allogeneic therapies more scalable and cost-effective for large-scale production.
Autoimmune diseases, with their slower progression and broader patient base, are driving the urgency for scalable, cost-effective solutions. Automation is key to transforming manual, labor-intensive autologous processes into streamlined, closed systems that reduce costs, ensure consistent quality, and meet rising demand. At the same time, continued progress in allogeneic therapies is essential to overcome hurdles like immune compatibility and durability. Both advances are likely to have particular benefits in autoimmune as well as oncologic indications.
By addressing these priorities and aligning regulatory frameworks, cell therapies can become widely accessible, affordable, and transformative for both oncological and non-oncological diseases, including autoimmune disorders.
