CD19-Targeted immunotherapies for Treatment of Pediatric t(8;21) Leukemia

Emergence of bispecific antibodies or CAR-T cells targeted against CD19 has significantly enhanced survival of patients with B-cell acute lymphoid leukemia. However, identifying a suitable target antigen for immunotherapy in acute myeloid leukemia (AML) has been challenging. Among different subtypes of AML, t(8;21) translocations have been associated with varying degrees of CD19 expression. This raises the question whether CD19 based immunotherapies can be repurposed for this subtype of AML. Therefore, we assessed the incidence of CD19 expression in pediatric patients in the Dutch NOPHO-DBH AML-2012 cohort, and the sensitivity of CD19-expressing AML cells towards blinatumomab, a CD19xCD3 bispecific antibody, or CD19-directed CAR-Ts. Eighteen out of 167 AML patients expressed CD19 of which 11 carried the t(8;21) translocation and expressed CD19 both on immature and mature sub-populations. Autologous killing assays with patient derived T-cells or CD19-directed CAR-Ts showed substantial sensitivity of t(8;21) AML towards T-cell mediated cytotoxicity. Our results therefore support clinical evaluation of blinatumomab and CAR-T 19 efficacy in pediatric patients with t(8;21) AML.

Publication History

Article published online:
12 May 2023