Acute lymphoblastic leukemia (ALL) is children’s most frequent kind of cancer. Despite advances in treatment, T-cell acute lymphoblastic leukemia (T-ALL) recurrence is associated with chemoresistance and a poor prognosis. The use of monoclonal antibodies is one method for overcoming this barrier. For a study, researchers showed that leukemic cells from T-ALL patients express surface CD38 and CD47, both of which are interesting targets for antibody treatment.
They evaluated the commercially available CD38 antibody daratumumab (Dara) in vitro and in vivo in conjunction with a proprietary modified CD47 antibody (Hu5F9-IgG2σ). The combination dramatically improved in vitro antibody-dependent cellular phagocytosis in T-ALL cell lines as well as random de novo and relapsed/refractory T-ALL patient-derived xenograft (PDX) samples compared to solo treatments. Similarly, increased antibody-dependent cellular phagocytosis was found when Dara was combined with pharmacologic suppression of CD47 interactions using a glutaminyl cyclase inhibitor.
Preclinical in vivo experiments employing T-ALL PDX samples in experimental minimal residual disease–like (MRD-like) and overt leukemia models demonstrated that CD47 blockage alone had high antileukemic effectiveness. When compared to solo therapies, combination therapy with Dara and Hu5F9-IgG2σ was required to significantly prolong survival in relapsed and severely resistant T-ALL PDX. The data indicated that combining CD47 blockage with Dara is a potential treatment for T-ALL, particularly in individuals with relapsed/refractory illness with a poor prognosis.