EHA 2025: Filling the gap for CAR T cell therapy

The Swiss Cancer Institute’s Young Oncology Academy (YOA) is a support and mentorship program for young oncologists. Academy participants are supervised by a renowned faculty member for almost a year and are required to write a review paper on a topic of interest. Today we present Dr. med. Francesco Manfrediʼs paper. He was a YOA participant in 2025 with the speciality hematology/cellular therapies and was mentored by Prof. Dr. med. Gabriela Baerlocher.

Chimeric antigen receptor (CAR) T cell therapy for hematological malignancies continues to expand rapidly, both in terms of approved products and new clinical indications. However, as applications broaden, the field increasingly faces delays in production and limited accessibility due to the constraints of current manufacturing processes.

Most approved CAR T cell therapies are autologous generated from a patient’s own T lymphocytes. This approach presents several challenges. In heavily pretreated patients or those with a high circulating tumor burden, it can be difficult to obtain enough viable T cells to expand and meet manufacturing requirements. In addition, CAR T cell production usually takes several weeks, exposing patients to the risk of disease progression before infusion. The process is also costly, labor-intensive, and centralized in a few specialized facilities, leading to long waiting times, logistical bottlenecks, and limited treatment availability as demand increases.

At the 2025 Annual Meeting of the European Hematology Association (EHA), a part of the cell therapy session focused on these manufacturing challenges, with a focus on the need to treat high-risk pa-tients (i.e. those heavily pretreated, with high tumor burdens, or rapidly progressing) and to make therapy accessible to more centers. Two presentations were particularly noteworthy in proposing innovative solutions to these problems.

Abstr. #S283:¹ allogeneic universal anti-CD7 CAR T cells for T-ALL

The first, presented by Dr. med. Xie Long and colleagues from Beijing (Abstr. #S283),reported the phase I/II clinical trial results on allogeneic universal anti-CD7 CAR T cell for T-cell acute lymphoblastic leukemia (T-ALL).^1,2 Unlike autologous products, a total of eight healthy donors provided all the batches for this «off-the-shelf» CAR T cells. To prevent CAR T cell rejection, graft-versus-host disease (GvHD), and fratricide among CAR T cells, the team used genome editing to eliminate surface expression of HLA molecules, the T-cell receptor, and CD7. This allogeneic approach dramatically shortened production timelines: the median time from screening to infusion was approximately three weeks, eliminating the need for bridging therapy. Because the therapy did not depend on harvesting viable T cells from each patient, no manufacturing failures occurred, and even patients with high circulating blast counts could be treated successfully.

Safety remains a key concern for allogeneic CAR T cell products, given potential risks of immune rejection and off-target effects. Dr. med. Long’s team reported a safety profile comparable to approved autologous CAR T cell therapies, including manageable rates of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hematotoxicity (ICAHT). Long-term safety assessment was limited, as all patients underwent consolidative allogeneic stem cell transplantation about 60 days post infusion, but no unexpected toxicities were observed.

The combined CAR T cell plus transplant approach achieved complete remission (CR) in approximately 60% of patients with a median follow-up of two years. Importantly, efficacy was maintained in patients with extramedullary disease – a sub-group typically associated with poor prognosis – with a 57% CR rate at the full therapeutic dose. These encouraging results represent a major milestone for allogeneic CAR T cell therapy, supporting its feasibility, safety, and potential scalability.

Abstr. #S281:³ optimizing autologous CAR T-cell production

The second notable presentation (Abstr. #S281), delivered by Dr. med. Mutsaers, focused on accelerating and decentralizing autologous CAR T cell production.³ The team introduced a novel manufacturing platform capable of generating a CAR T cell product within seven days of leukapheresis, significantly faster than the traditional multi-week process.

This was achieved by shortening the culture period and decentralizing production, thereby eliminating the need for shipping of patient material to the production center. The resulting CAR T cells maintained an early T cell memory phenotype, which may contribute to improved persistence and long-term disease control.

Early clinical results showed a favorable safety profile, with low rates of severe CRS and ICANS, possibly reflecting the slower, more sustained cytotoxic activity of memory T cells. Efficacy was evaluated in patients with both aggressive (DLBCL, MCL) and indolent (FL, MZL) B-cell non-Hodgkin lymphomas. At dose level 2, responses in DLBCL were comparable to those seen with approved CAR T cell products, while outcomes in indolent lymphomas were particularly favourable.

Whether these superior responses are due to enhanced CAR T cell persistence remains under investigation, as longer-term follow-up is needed, especially in indolent lymphomas where relapses can occur months or years after treatment.

Conclusio

Together, these two studies exemplify the innovation currently shaping the CAR T-cell field. The allogeneic «off-the-shelf» approach offers a scalable solution to production bottlenecks, while accelerated, decentralized manufacturing could make autologous therapies faster and more widely accessible. The findings presented at EHA 2025 underscore the field’s ongoing evolution toward making CAR T cell therapy not only more efficient but also more clinically impactful. Continued research will determine how these advances translate into broader real-world adoption and improved patient outcomes.