Professor Arnon Nagler from the Sheba Medical Center in Tel Aviv, Israel, discussed the paradigm shift of applying CAR-T cell therapy, a cornerstone of hematologic oncology, to the complex world of autoimmune diseases.Highlighting Sheba’s expanding clinical trials in lupus and myositis, Prof. Nagler articulated that this transition represents a “different ball game,” emphasizing the critical importance of a nuanced approach to safety and patient monitoring.
Unlike in oncology, patients with autoimmune diseases are typically younger, have not been exposed to prior chemotherapy, and present unique safety considerations.Prof. Nagler explained that defining durable remission requires meticulous monitoring of specific biomarkers, such as complement and double-stranded DNA levels in lupus, alongside clinical scales and organ function assessments. His team also tracks CAR-T cell persistence and expansion, prepared to biopsy affected organs in case of toxicity.
A key theme was the collaborative synergy currently required between hematologists, who possess deep experience with CAR-T cell logistics and toxicities, and autoimmune specialists, who have intimate knowledge of the patient and disease progression. However, Prof. Nagler envisions a future where autoimmune physicians will independently manage these therapies as they become more established.
Looking ahead, he touched on next-generation technologies, from the evolution of in-house academic CAR-T production to automated manufacturing and the ongoing debate between autologous and allogeneic (“off-the-shelf”) products. While allogeneic therapies offer logistical advantages, more safety data is needed. Concluding his remarks, Prof. Nagler stressed that while the preliminary data is highly encouraging, the field is only at “the beginning of an exciting era,” underscoring the need for larger, controlled studies to unlock the full potential of cellular therapies across disease boundaries.
