CD19 mutations found in CD19 negative relapse to CART-19 in ALL patients

While Chimeric Antigen Receptor T cell therapy has demonstrated remarkable success for CD19 positive B cell malignancies, relapse poses a significant threat. We studied mechanisms of CD19 negative relapse and found acquired genetic mutations and loss of heterozygosity in CD19 at relapse. The mutations are predicted to lead to the loss of cell surface CD19 and epitope suggesting the potential for retreatment with an alternate targeting or combination CAR approach.