Lei Xue1, Yan Hu1, Jian Wang1, Xin Liu1, Xingbing Wang1,2. 1. Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Sciences and Technology of China, Hefei, Anhui 230001, People's Republic of China. 2. Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
Abstract
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.
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.
Entities:
Keywords:
acute myeloid leukemia; immunotherapy; tumor-associated antigen-specific T cells
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