T-cell adoptive immunotherapy for acute lymphoblastic leukemia

Abstract

Substantial progress has been made in the treatment of precursor B-cell acute lymphoblastic leukemia (B-ALL), but recurrent disease remains a leading cause of death in children due to cancer and outcomes for adults with B-ALL remain poor. Recently, complete clinical responses have been observed in small numbers of patients with B-ALL treated with adoptive immunotherapy using T cells genetically engineered to express chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule present in essentially all cases of B-ALL. Preclinical data suggest that CARs targeting CD22, another antigen present in the majority of B-ALL cases, are similarly potent. Several clinical studies already under way will soon more clearly define the rate of response to this novel therapy in B-ALL. Further work is needed to identify optimal platforms for CAR-based adoptive immunotherapy for leukemia, to establish guidelines for managing toxicity, and to determine whether the remissions induced by this approach can be rendered durable.

Figure 1.. Bioluminescent imaging results.

NSG-immunodeficient mice were inoculated on day 0 with 5 × 10⁵ NALM-6-GL cells and then, on day 3, received 1.5 × 10⁷ CAR-modified T cells as designated. Mock recipients received 1.5 × 10⁷ total cells. Transduction efficiency was ~ 40% in both CAR groups. Mock-transduced cells were activated and expanded but were not exposed to viral vector. Bioluminescent imaging using standard techniques at the designated time points demonstrates clearance of the leukemia by day 8. All CAR-treated mice were long-term leukemia-free survivors, whereas all mock-treated mice succumbed to leukemia.