Complex evaluation of human monocyte-derived dendritic cells for cancer immunotherapy

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Authors

VOPĚNKOVÁ Kateřina MOLLOVÁ Klára BUREŠOVÁ Ivana MICHÁLEK Jaroslav

Year of publication 2012
Type Article in Periodical
Magazine / Source Journal of Cellular and Molecular Medicine
MU Faculty or unit

Faculty of Medicine

Citation
Web http://onlinelibrary.wiley.com/doi/10.1111/j.1582-4934.2012.01614.x/abstract
Doi http://dx.doi.org/10.1111/j.1582-4934.2012.01614.x
Field Oncology and hematology
Keywords cancer immunotherapy; cytotoxicity; dendritic cell; interleukin-12; maturation; migration
Attached files
Description Dendritic cell (DC) immunotherapy is capable of generating tumour-specific immune responses. Different maturation strategies were previously tested to obtain DC capable of anti-cancer responses in vitro, usually with limited clinical benefit. Mutual comparison of currently used maturation strategies and subsequent complex evaluation of DC functions and their stimulatory capacity on T cells was performed in this study to optimize the DC vaccination strategy for further clinical application. DC were generated from monocytes using granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, pulsed with whole tumour cell lysate and then matured with one of five selected maturation strategies or cultured without additional maturation stimulus. DC were characterized with regard to their surface marker expression, cytokine profiles, migratory capacity, allogeneic and autologous T cell stimulatory capacity as well as their specific cytotoxicity against tumour antigens. We were able to demonstrate extensive variability among different maturation strategies currently used in DC immunotherapeutic protocols that may at least partially explain limited clinical benefit of some clinical trials with such DC. We identified DC matured with interferon-gamma and lipopolysaccharide as the most attractive candidate for future clinical trials in cancer immunotherapy.
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