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Biological properties of leukemia cell-derived exosome and anti-leukemia effects of its sensitized DCs
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Abstract:
Objective:To explore the biological properties of leukemia cell-derived exosomes (LEXs) and the anti-leukemia immunological effect of LEX-sensitized dendritic cells (DCs). Methods: LEX from BCR-ABL positive leukemia K562 cells was separated and purified by ultracentrifugation. The expressions of heat shock protein 70 (HSP70) and BCR-ABL were investigated by immuno-electron microscopy and Western blotting. The kinetics of LEXK562 targeted binding to DCs was examined by laser scanning confocal microscopy and flow cytometry. The anti-leukemia immunological effect of LEX and its sensitized DCs was explored by LDH release assay and in vivo mouse model studies. Results: K562 cell-derived exosomes (LEXK562) had cystic structures between 50 and 100 nm diameter as the other cell-derived exosomes, and expressed K562 cell specific proteins, HSP70 and BCR-ABL. LEXK562 could target and bind DCs in vitro, and reached a plateau after 3 to 4 h of co-culturing. LEXK562 uptaken in DCs was quite stable for over 72 h. Cytotoxic T lymphocytes (CTLs) induced by LEXK562-sensitized DCs (DC/LEXK562) could effectively kill K562 target cells, and their cytotoxicity was significantly higher than that of CTLs induced by LEXK562 (\[68.6±5.7\]% vs \[22.5±2.9\]%, P<0.01) at an effector to target ratio of 50∶1. Furthermore, the in vivo study demonstrated that the incidence of tumor in mice incubation with leukemia L1210 cells after being immunized with L1210-derived exosomes (LEXL1210) was significantly higher than that of LEXL1210-sensitized DCs (\[54.17±8.33\]% vs \[16.67±4.18\]%, P<0.05). Conclusion: LEX expresses antigens associated with leukemia cells and can target bind DCs in vitro. LEX-sensitized DCs can induce a stronger anti-leukemia immunological effect.
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Projectsupported by the National Natural Science Foundation of China (No. 81070432), and the Pujiang Program for Talents of Shanghai (No. 08PJ1407600)
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