Cellular Therapy Manufacturing for Hematological Diseases: Challenges, Innovations and Future Directions

Cellular and gene therapies have become established treatment options for hematological diseases, including rare and aggressive neoplasms. The clinical success of CAR T cell therapies has fundamentally altered the treatment landscape of hematological malignancies, offering deep and durable responses in patient populations with limited alternatives. Alongside CAR T cells, emerging platforms, including engineered T cell receptor (TCR), natural killer (NK) cell, haematopoietic stem cell, dendritic cell and cancer vaccine-based therapies, continue to expand the therapeutic arsenal. Together, these modalities hold the potential to progressively reduce dependence on conventional chemotherapy, positioning immunotherapy, cellular and gene therapy, and targeted small-molecule approaches as central pillars of haematological oncology care.Despite remarkable clinical responses, translating cellular therapies from bench to bedside remains constrained by significant manufacturing challenges. The production of established commercial products such as CAR T cells is inherently complex: it is patient-specific, labour-intensive and dependent on multiple ex vivo steps, including cell selection and activation, transgene delivery, expansion, viability assessment and functional release testing. Strict Good Manufacturing Practice (GMP) compliance, complex cryopreservation and cold-chain logistics, and evolving regulatory frameworks add to the operational burden.Meeting the growing clinical demand for these therapies requires a fundamental shift in how they are manufactured. The field is increasingly moving toward automated, scalable and standardised platforms. Closed-system bioreactors, advanced gene-editing tools, allogeneic and off-the-shelf cell sources, real-time process analytical technologies, and in vivo manufacturing strategies are among the most promising approaches for addressing bottlenecks in reproducibility, cost and broader patient access. Integrating artificial intelligence (AI) and digital twin modelling into process development offers additional potential to accelerate optimisation and reduce manufacturing variability.This Research Topic aims to consolidate the latest advances in manufacturing across CAR T cells and other emerging cellular therapies for hematological diseases. It seeks to provide deeper insight into cell engineering, novel product development and practical strategies to address manufacturing complexity at every stage of the production chain. We invite submissions on topics including, but not limited to:• Autologous and allogeneic cell production • Ex vivo and in vivo manufacturing strategies• Viral and non-viral gene delivery systems• Optimised viral vector design and scalable production• Gene-editing platforms and multiplex cell engineering• Vein-to-vein logistics optimization• Automated, closed bioreactor platforms • Real-time process monitoring for cell expansion and phenotype control Topic editors: Stella Bouziana, Volker Huppert Source: https://www.frontiersin.org/research-topics/83333/cellular-therapy-manufacturing-for-hematological-diseases-challenges-innovations-and-future-directions