Innovative Dual-Target CAR-T Cells Show Promise Against T-ALL Leukemia in Preclinical Studies

Recent advances in immunotherapy have led to the development of chimeric antigen receptor T (CAR-T) cell therapies, which have shown remarkable success in treating various blood cancers. However, their application to T-cell acute lymphoblastic leukemia (T-ALL), a highly aggressive blood cancer affecting both children and adults, has been challenging due to the difficulty in distinguishing cancerous T-cells from healthy ones.

T-ALL arises from the abnormal proliferation of immature T-lymphocytes, leading to the disruption of normal immune function. While children with T-ALL have a cure rate of over 80%, adults face a lower rate of around 40%, often accompanied by relapse after conventional chemotherapy.

In a significant breakthrough, researchers at the Josep Carreras Leukaemia Research Institute, in collaboration with Dr. Diego Sánchez and biotech partner OneChain Immunotherapeutics, have identified specific markers on leukemic T-cells that are absent or minimally expressed in healthy T-cells. These markers are CD1a and CCR9 proteins, which are predominantly present on T-ALL cells across most patients.

Using this discovery, the team engineered dual CAR-T cells targeting both CD1a and CCR9. Laboratory experiments demonstrated that these engineered cells could effectively recognize and eliminate leukemic cells expressing either or both markers. Notably, this dual-target approach showed increased efficacy compared to therapies targeting only one antigen.

Furthermore, these dual CAR-T cells exhibited a favorable safety profile by sparing healthy T-lymphocytes and other bone marrow cells, reducing the risk of fratricide and off-target effects. The findings, published in the Journal of Hematology & Oncology, suggest that this innovative strategy could provide a more effective and safer treatment for T-ALL patients, including those with heterogeneous disease profiles.

This research represents a promising step toward the clinical development of a specialized cell therapy for T-ALL, which could significantly improve outcomes and reduce relapse rates in both children and adults. As the therapy advances into clinical trials, it holds the potential to become the first effective targeted treatment specifically for T-ALL.