Dendritic cells stimulate the expansion of PML-RAR alpha specific cytotoxic T-lymphocytes: its applicability for antileukemia immunotherapy.
Dendritic cells (DC), the most potent "professional" antigen-presenting cells, hold promise for improving the immunotherapy of cancer. In this study, we investigated the ability of normal donor DC pulsed ex vivo with 12 mer PML-RAR alpha (A) peptide (SGAGEAAIETQS) to generate peptide specific autologous cytotoxic T-lymphocytes. The peptide pulsed DC-primed peripheral blood lymphocytes (PBL) displayed significantly higher cytotoxic activity compared with that of peptide non-pulsed DC-primed PBL against peptide-pulsed autologous macrophages (P<0.001). Both CD8+ and CD4+ T lymphocytes were involved in the effector cell populations. The PML-RAR alpha peptide-pulsed DC-primed T-cells were significantly superior in their production of GM-CSF and TNF-alpha, compared with peptide non-pulsed DC-primed T-cells. These intriguing preclinical studies, suggest that PML-RAR alpha pulsed-DC could be a promising immunotherapeutic modality for patients with acute promyelocytic leukemia.
Osman
Y
Y
First Dept. of Internal Medicine, Faculty of Medicine, Niigata University, Japan.
Takahashi
M
M
Zheng
Z
Z
Toba
K
K
Liu
A
A
Furukawa
T
T
Narita
M
M
Aizawa
Y
Y
Koike
T
T
Shibata
A
A
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D015473:Leukemia, Promyelocytic, Acute / Q000276:immunology / Q000628:therapy*; D008264:Macrophages / Q000276:immunology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics*; D010446:Peptide Fragments / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016207:Cytokines; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010446:Peptide Fragments; D011994:Recombinant Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein