Phase I trial: Donor-derived CD6-CAR Tregs in chronic GvHD

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Amandeep Salhotra reported results from a phase I trial (NCT05993611) evaluating donor-derived CD6-chimeric antigen receptor (CAR) regulatory T cells (Tregs) in patients with steroid-dependent or refractory chronic graft-versus-host disease (cGvHD) post allogeneic hematopoietic stem cell transplantation (allo-HSCT; N = 6). The primary endpoint was safety, by evaluation of toxicities.   

Key data: No dose-limiting toxicities (DLTs), cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or GvHD flare-up occurred. Grade 3 adverse events (AEs) included lymphopenia (n = 2) and hypertension (n = 2). Five of six patients with ≥3 months’ follow-up achieved partial response (PR) with continued failure-free survival (FFS). CD6-CAR Tregs demonstrated persistence in skin biopsies for up to 2 months after infusion. 

Key learning: This phase I trial demonstrates that allogeneic donor-derived CD6-CAR Tregs can be successfully manufactured and administered to patients with cGvHD without significant toxicity, with early evidence of clinical efficacy supporting further investigation of this novel cellular immunotherapy approach.