The new hope 'made in Spain' against leukemia: the first dual CAR-T therapy

The Aragón Health Research Institute has designed a therapeutic strategy using CAR-T cells against T-cell acute lymphoblastic leukemia, which has demonstrated "high efficacy" and a safety profile, facilitating the possibility of short-term clinical development . The work, published in the Journal of Oncology and Hematology, presents CAR-T cells that target two specific markers of this type of leukemia, the Josep Carreras Institute reported in a statement on Monday.

T-cell lymphoblastic leukemia ( T-ALL ) is a highly aggressive type of blood cancer that can occur in children (with an 80% cure rate) and adults (with a 40% cure rate and a higher risk of relapse). It is characterized by defects in the maturation of T cells , key immune cells in the fight against infection and cancer, which instead of performing their intended function, multiply uncontrollably in the bone marrow .

CAR-T cell treatments , which have had very good results in other blood cancers, have not been effective in T-ALL because the affected cells are precisely the same ones used in these therapies: T lymphocytes. Therefore, finding markers that are present in tumor lymphocytes and not in healthy T lymphocytes, thus avoiding the "fratricidal" attack, is especially difficult.

Researchers have shown that the CD1a and CCR9 proteins are found on leukemia cells in most T-ALL patients, but not on healthy cells or other cells to any significant extent, which would allow for the distinction between T cells; with this finding, the scientific team has developed and tested in the laboratory the " first dual CAR-T therapy against T-ALL ."

The results show that these new cells attack cells that display both CD1a and CCR9 —or just one of the two—but not healthy cells or cells from other parts of the body to any significant extent, and that they are able to keep 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 were focused on only one of the two, and expands the range of use to patients with heterogeneous T-ALL , in which the amounts of the two targets are variable in the leukemic cells.

The results, together with previous evidence, pave the way for clinical development of what could be, in the medium term, the first cellular therapy against T-ALL.

The Aragón Health Research Institute has designed a therapeutic strategy using CAR-T cells against T-cell acute lymphoblastic leukemia, which has demonstrated "high efficacy" and a safety profile, facilitating the possibility of short-term clinical development . The work, published in the Journal of Oncology and Hematology, presents CAR-T cells that target two specific markers of this type of leukemia, the Josep Carreras Institute reported in a statement on Monday.