A scientific team from the Josep Carreras Leukaemia Research Institute, the Aragon Health Research Institute, and the biotechnology company OneChain Immunotherapeutics has developed a new therapy based on CAR-T cells designed to simultaneously target two specific markers of T-cell acute lymphoblastic leukemia (T-ALL): the proteins CD1a and CCR9. Published in the Journal of Oncology and Hematology, the preclinical results of the therapy, named OC-1d and already incorporated into the company’s pipeline, show high efficacy and an excellent safety profile, reinforcing its potential to advance toward clinical trials in the near future.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer that affects both children and adults and is characterized by errors in the maturation of T lymphocytes — key immune cells in the fight against infections and cancer — which, instead of fulfilling their function, multiply uncontrollably in the bone marrow. While the cure rate in children exceeds 80%, in adults it stands at around 40% and is associated with a high likelihood of relapse after chemotherapy.

Unlike other leukemias, T-ALL poses a major challenge for CAR-T therapies, as these are based on T lymphocytes — the same type of cell that proliferates malignantly in this disease. This makes it difficult to identify specific targets that allow tumor cells to be attacked without harming healthy ones.

The research carried out by the team led by Dr. Pablo Menéndez, from the Josep Carreras Leukaemia Research Institute, with the support of Dr. Diego Sánchez, ARAID researcher at the Aragon Health Research Institute, and the biotechnology company OneChain Immunotherapeutics — a spinoff of the Josep Carreras Institute — shows that the proteins CD1a and CCR9 are present in the leukemic cells of most T-ALL patients but not appreciably in healthy cells or other parts of the body.

In this context, the researchers have developed and tested in the laboratory the first dual CAR-T therapy against T-ALL. Experimental results show that these new CAR-T cells attack cells expressing both CD1a and CCR9, or just one of the two, and are capable of keeping the disease under control in both in vitro and in vivo models. The ability to target two antigens simultaneously makes this new therapy significantly more effective than targeting just one, as demonstrated in the study, and broadens its applicability to patients with heterogeneous T-ALL, in which the levels of the two targets vary among leukemic cells.

These new dual CAR-T cells against CD1a and CCR9 spare healthy T lymphocytes, as well as themselves and other bone marrow cells, thus presenting an excellent safety profile. The results, together with previous evidence from this same research team and others internationally, pave the way for the clinical development of what could become, in the medium term, the first cell therapy against T-ALL.

» Article of reference: Tirado, N., Fidyt, K., Mansilla, M.J. et al. “CAR-T cells targeting CCR9 and CD1a for the treatment of T cell acute lymphoblastic leukemia”. J Hematol Oncol 18, 69 (2025). doi: https://doi.org/10.1186/s13045-025-01715-0

» Link to the news: Josep Carreras Leukaemia Research Institute [+]