Vaccine · 2014
Development and immunological evaluation of HLA-specific chronic myeloid leukemia polyepitope vaccine in Chinese population.
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Dong Wenhao, Zhang Jingru, Shao Na, Tian Tian, Li Lu, Jian Jimo, Zang Shaolei, Ma Daoxin, Ji Chunyan
Аннотация
BACKGROUND: BCR/ABL and Wilms' tumor 1 (WT1) are an ideal tumor associated antigens which can be used to develop a potential chronic myeloid leukemia (CML) dentritic cell (DC) vaccine. Here, we constructed a novel polyepitope vaccine which used recombinant lentiviral vector carrying BCR/ABL and WT1 genes, and determined the immunological effects of this vaccine in vitro.
METHODS: The DC vaccine was constructed using lentiviral vector transduced DCs. T lymphocytes were stimulated with DC vaccine and then co-cultured in vitro with peripheral blood mononuclear cells (PBMCs) from CML or ALL patients, respectively. The cytotoxicity of proliferous cytotoxic T lymphocytes (CTLs) was determined by the LDH assay. The IFN-γ production of CTLs was detected using ELISPOT assay.
RESULTS: We constructed an lentiviral vector encoding 50 different epitopes from BCR/ABL and WT1 antigens, and transferred it into DCs to prepare the DC vaccine successfully. The in vivo stimulation of CTLs with this DC vaccine were proved to show strong cytotoxicity and produce high level of IFN-γ.
CONCLUSIONS: The novel recombinant lentiviral polyepitope DC vaccine is a promising candidate for clinical trials and may be an effective approach for CML immunotherapy.
METHODS: The DC vaccine was constructed using lentiviral vector transduced DCs. T lymphocytes were stimulated with DC vaccine and then co-cultured in vitro with peripheral blood mononuclear cells (PBMCs) from CML or ALL patients, respectively. The cytotoxicity of proliferous cytotoxic T lymphocytes (CTLs) was determined by the LDH assay. The IFN-γ production of CTLs was detected using ELISPOT assay.
RESULTS: We constructed an lentiviral vector encoding 50 different epitopes from BCR/ABL and WT1 antigens, and transferred it into DCs to prepare the DC vaccine successfully. The in vivo stimulation of CTLs with this DC vaccine were proved to show strong cytotoxicity and produce high level of IFN-γ.
CONCLUSIONS: The novel recombinant lentiviral polyepitope DC vaccine is a promising candidate for clinical trials and may be an effective approach for CML immunotherapy.
Предметные рубрики MeSH
AdultAgedAntigens, NeoplasmAsian PeopleCancer VaccinesCells, CulturedDendritic CellsEpitopesFemaleFusion Proteins, bcr-ablGenes, MHC Class IGenes, MHC Class IIGenetic VectorsHEK293 CellsHumansImmunotherapyInterferon-gammaLentivirusLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukocytes, MononuclearMaleMiddle AgedT-Lymphocytes, CytotoxicWT1 Proteins