A new cell therapy for leukemia shows high efficacy and safety in the laboratory.

Scientists from the Josep Carreras Leukemia Research Institute and the Aragón Health Research Institute have just presented a new strategy for combating T-cell acute lymphoblastic leukemia. The new therapy is based on the use of CAR-T cells engineered to target two specific markers of this type of leukemia: the CD1a and CCR9 proteins. Preclinical results of this new drug demonstrate its high efficacy and excellent safety profile, facilitating its potential for short-term clinical development.

La cell lymphoblastic leukemia T-cell lymphocytes (T-ALL) are a highly aggressive type of blood cancer that can occur in both childhood and adulthood. It is characterized by failures in the maturation of T lymphocytes, key immune cells in the fight against infections and cancer. Instead of performing their intended function, they multiply uncontrollably in the bone marrow. While the cure rate in children exceeds 80%, in adults it is 40% and is associated with a high probability of relapse after chemotherapy..

And yet, advances in the field of Immunotherapy, especially CAR-T cell treatments that have been so successful in other blood cancers, has not yet reached T-ALL. This is precisely because the affected cells are the same ones used in these therapies, T lymphocytes, so finding markers that are in tumor lymphocytes and not in healthy T lymphocytes, thus avoiding fratricidal attack, is especially complicated.

Finding a way to distinguish leukemic T cells from the rest is exactly what the team at the Dr. Pablo Menéndez, from the Josep Carreras Leukemia Research Institute, with the support of Dr. Diego Sánchez, ARAID researcher from the Aragón Health Research Institute, and the biotechnology company OneChain Immunotherapeutics, a spin-off of the Josep Carreras Institute. Through their research, they have demonstrated that the CD1a and CCR9 proteins are found in the leukemic cells of most T-ALL patients, but not in healthy cells or in other parts of the body to any significant extent.

Thanks to this discovery, published in the Journal of Oncology and Hematology, one of the best in the field, the scientific team has been able to develop and test in the laboratory the first dual CAR-T therapy against T-ALL. The experimental results demonstrate that these new CAR-T cells attack cells that display both CD1a and CCR9, or only one of the two, and are capable of keeping the disease at bay in both in vitro and in vivo models.

The ability to attack two targets at once makes this new therapy much more effective than if it only focused on one of the two, as demonstrated in the study, and expands the range of use to patients with heterogeneous T-ALL, in which the amounts of the two targets are variable in leukemic cells.

Furthermore, unlike previous attempts, these new dual CAR-T cells against CD1a and CCR9 spare both healthy T cells and themselves and other bone marrow cells, thus presenting an excellent safety profile. These results, along with previous evidence from research by this same scientific team and others internationally, pave the way for the clinical development of what could be, in the medium term, the first cellular therapy against T-ALL.

This work has received funding from the Spanish Government (State Research Agency, Carlos III Health Institute, Ministry of Science and Innovation), the Generalitat de Catalunya (Catalan Government), and the European Union, as well as from the private entities Josep Carreras Foundation, Obra Social La Caixa, the Spanish Association Against Cancer, Unoentrecienmil, and the Merck Foundation. No generative AI tools were used in the writing of this communication.

Reference article:

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