Italian researchers have demonstrated proof-of-concept for an innovative immunotherapeutic approach to the treatment of T-cell acute lymphoblastic leukemia (T-ALL) using a monoclonal antibody and two bispecific T-cell engagers. The preclinical study appears in the Journal for ImmunoTherapy of Cancer.

Targeting UMG1, a unique epitope of CD43 that is highly expressed in cortical-derived T-ALL cells, the research team, led by Pierfrancesco Tassone, PhD, of the Magna Graecia University of Catanzaro, Italy, developed an afucosylated form of the humanized mAb UMG1 and two bispecific T-cell engagers that simultaneously bind to the UMG1 epitope on T-ALL cells and CD3ε to induce cell-mediated killing of epitope-expressing leukemic cells.

No effective therapy is currently available for relapsed or refractory T-ALL, an aggressive disease derived from the abnormal proliferation of aberrant intra-thymic T-cell progenitor cells. 

“To the best of our knowledge, our findings describe the first [BiTE] targeting T-ALL with a potential very low risk of T-cell immunosuppression,” Tassone and his coauthors write. They conclude that “our findings, including the safe UMG1-epitope expression profile, provide a framework for the clinical development of these innovative immune-therapeutics for this still orphan disease.”

• Caracciolo D, Riillo C, Ballerini A, et al. Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia. J Immunother Cancer. 2021;9(2):e002026. doi:10.1136/jitc-2020-002026

Tags: BiTEs, cell therapy, T-ALL, promising, new approach, orphan disease