Rui Deng1, Fang-Yi Fan1, Hai Yi1, Fang Liu1, Guang-Cui He1, Hao-Ping Sun1, Yi Su1. 1. a Hematology Department and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center , Cheng Du Military General Hospital of PLA , Cheng Du , People's Republic of China.
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.
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 humanAML 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.
Entities:
Keywords:
Programmed death receptor-1; acute myeloid leukaemia; adoptive cytotoxic T cell