Introduction: The anti-CD19 immunotherapy for the treatment of B-precursor acute lymphoblastic leukemia (B-ALL) underwent an expansion in the last decade. CD19 is widely expressed on B-ALL and nearly ideal for immunotherapy because of strong 'on target' ─ but manageable 'off target' effects.
Areas covered: We review the major advances in the field, including data on CD19 monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engaging antibodies and adoptive cellular therapies such as chimeric antigen receptor T cells (CAR-Ts). We discuss novel strategies on approved anti-CD19 immunotherapies. The focus is on experimental anti-CD19 antibodies or CAR-Ts, which might overcome the limitations of toxicity, rapid clearance or resistance.
Expert opinion: The potential of new anti-CD19 antibodies in ALL is limited. The most promising results were achieved with novel cellular constructs. Bi- or multi-specific CAR-Ts might overcome the immune escape by antigen loss. Modified constructs with lower peak expansion or longer persistence provide better control of the toxicity and might improve the efficacy. Finally, the allogeneic 'off the shelf' constructs from healthy donors avoid the time-consuming preparation and the exhaustion of immune cells.
Keywords: Acute lymphoblastic leukemia; CAR-T; CD19; antibody drug conjugates; bispecific antibody; blinatumomab; chimeric antigen receptor; multi-CAR-Ts.