A new T cell-redirecting strategy for the treatment of relapse/refractory T cell acute lymphoblastic leukemia

T cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy resulting from the transformation and accumulation of T lineage precursor cells in the bone marrow (BM). Relapse/refractory (R/R) T-ALL remains a challenge with a particularly poor outcome, without curative options beyond hematopoietic stem cell transplantation and conventional chemotherapy, in contrast to B cell malignancies where multiple chimeric antigen receptor-T (CAR-T) strategies exist. The main obstacle to the development of CAR-T therapies for T-ALL is the shared expression of target antigens in leukemic blasts and healthy T cells, leading to fratricide and life-threatening T cell aplasia.

Here, we have identified a novel target antigen for the immunotherapy of T-ALL, expressed across all developmental stages of the disease, in a large cohort of primary samples. Notably, this antigen demonstrated a very safe profile in hematopoietic and non-hematopoietic tissues, as evidenced by flow cytometry and scRNA-seq analyses. After characterization of our candidate target, we proceeded to the generation of an efficient and safe CAR-T cell strategy for the treatment of R/R T-ALL.

Publication History

Article published online:
17 May 2022