T cells targeting multiple tumor-associated antigens as a postremission treatment to prevent or delay relapse in acute myeloid leukemia

摘要

Background: Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. Tumor-associated antigen-specific cytotoxic T lymphocyte (TAA-CTLs)-based therapy was introduced and increasingly used clinically to kill tumor cells via tumor antigen activation. Method: In this study, we expanded autologous lymphocytes reactive to five TAA (NY-ESO-1, MAGE-A3, WT1, Survivin, and PRAME) and evaluated its safety and efficacy in 9 patients with AML at high risk of relapse. Results: Before first TAA-CTL infusion, 5 patients were minimal residual disease (MRD) positive, whereas 4 were MRD negative. Patients received TAA-CTL infusion for 1–3 times. None of them had obvious adverse reactions during or post the infusion. Of the 4 MRD-negative patients who were infused with TAA-CTLs, one developed relapsed disease. Among 5 MRD+ patients, there was a demonstrable antileukemic effect of the TAA-CTLs alone without any concomitant chemotherapy in 2 patients, as demonstrated by the negative of MRD in bone marrow after TAA-CTL infusion. Conclusions: In summary, we have observed preliminary indications of activity and safety after administration of autologous TAA-CTLs in patients with AML. The ultimate question of clinical efficacy, however, will need to be addressed in a larger trial with larger homogeneous patient population.