T cells targeting multiple tumor-associated antigens as a postremission treatment to prevent or delay relapse in acute myeloid leukemia
Authors Xue L, Hu Y, Wang J, Liu X, Wang X
Received 14 February 2019
Accepted for publication 12 June 2019
Published 16 July 2019 Volume 2019:11 Pages 6467—6476
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Dr Eileen O'Reilly
Lei Xue,1 Yan Hu,1 Jian Wang,1 Xin Liu,1 Xingbing Wang1,2
1Department 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; 2Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China
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.
Keywords: tumor-associated antigen-specific T cells, immunotherapy, acute myeloid leukemia
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