PD-1 blockade potentially enhances adoptive cytotoxic T cell potency in a human acute myeloid leukaemia animal model. Issue 10 (26th November 2018)

• Record Type: Journal Article
• Authors: Deng, Rui; Fan, Fang-yi; Yi, Hai; Liu, Fang; He, Guang-cui; Sun, Hao-ping; Su, Yi
• Is Part Of: Hematology. Volume 23:Issue 10(2018)
• Page Start: 740
• Page End: 746
• Publication Date: 2018-11-26
• Subjects: Programmed death receptor-1 -- adoptive cytotoxic T cell -- acute myeloid leukaemia; Blood -- Diseases -- Periodicals; Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; 616.15005
• DOI: 10.1080/10245332.2018.1486357
• Languages: English
• ISSNs: 1024-5332

Abstract

ABSTRACT: Objectives: Acute myeloid leukaemia (AML) is a malignant haematological disease that remains difficult to cure. Cytotoxic T cell (CTL) adoptive infusion therapy may be conducive to tumour remission by boosting physical immunity. Furthermore, programmed death receptor-1 (PD-1) blockade immunotherapy has shown tremendous success in many cancer therapies. Method: We attempted to combine these two immunotherapy strategies to intervene in AML by generating AML cellspecific cytotoxic T lymphocytes in vitro and in vivo with an AML cell strain expressing specific antigens. Results: First, we observed that peripheral blood mononuclear cells (PBMCs) could be induced to generate large numbers of CD8 + CTL cells through immune stimulation. In addition, these CD8 + cells could effectively recognize a human AML cell line and exert cytotoxicity. In animal tests, PD-1 blockade combined with CTL infusion could induce significantly more AML tumour reduction than either treatment alone. This synergistic effect was thought to be connected to immune modulation enhancement, as regulatory T cells (Tregs) in the peripheral blood (PB) were found to be suppressed. Conclusions: This finding suggested the potential application of PD-1 blockade in AML. The present work demonstrated an excellent synergistic tumour therapeutic effect of PD-1 blockade and CTL therapy compared with either treatment alone.