A novel alpaca-derived, nanobody-based, anti-CD5 bispecific epitope CAR T-cell vector showed excellent antigen specificity, cytotoxicity, and efficacy for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (ALL), according to preclinical and phase 1/2 data presented at the 2026 EHA Congress in Stockholm, Sweden.
The nanobody-based CD5 CAR T-cells had superior antigen-dependent activation compared with humanized CD5 CAR T-cells, said lead author, Jing Pan, MD, PhD, of the Chinese Academy of Medical Sciences and Peking Union Medical College in Tianjin, China.
The researchers constructed the CD5 CAR T-cell vector using a 15 kDa alpaca VHH antibody to improve T-cell expansion compared with their previous humanized CD5 CAR T-cell construct.
After successful preclinical in vitro and murine model evaluation, the nanobody-based CD5 CAR T-cell was trialed in six patients with relapsed or refractory T-cell ALL, four of whom were refractory to prior anti-CD7 CAR T-cell therapy.
Adverse events within 30 days included grade 1 cytokine release syndrome in all six patients, grade 2 immune effector cell-associated neurotoxicity syndrome in 1 patient, and grade 1 to 2 graft-versus-host disease in two patients. All patients achieved complete remission by day 30, and by day 90, five patients had continued to allogeneic stem cell transplantation and four patients had negative measurable residual disease. One patient had CD5–diminished relapse at day 88 and another had CD5–negative relapse at day 45 and died on day 51. The peak expansion of CAR T-cells was at day 10 (range, 7-21).
The trial was ongoing, and would generate further data on long-term efficacy, safety, and immune reconstitution, wrote Dr. Pan and colleagues.
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