Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model

BMC Cancer

Research Article

Ivana Jochmanová¹  Hana Husníková²  Jan Ženka²  Andra Vieru²  Zuzana Kumžáková²  Gabriela Krejčová²  Veronika Caisová²  Nikol Vácová²  Lucie Paďouková²  Jindřich Chmelař²  Simona Glaserová²  Jan Kopecký³  Katherine I. Wolf⁴ 

[1] 1st Department of Internal Medicine, Medical Faculty of P. J. Šafárik University in Košice, Košice, Slovakia;Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic;Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic;Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, v.v.i., České Budějovice, Czech Republic;University of Michigan Medical Center, Ann Arbor, MI, USA;

关键词: Cancer immunotherapy;    Innate immunity;    Melanoma;    Neutrophils;    Resiquimod;    Mannan;    Phagocytosis;   

DOI  :  10.1186/s12885-016-2982-x

 received in 2016-04-23, accepted in 2016-11-30,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundUsing killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19th century. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans.MethodsB16-F10 murine melanoma model was used. For the stimulation of phagocytosis, mannan or N-formyl-methionyl-leucyl-phenylalanine, was covalently bound to tumor cells or attached using hydrophobic anchor. The following agonists of Toll-like receptors were studied: monophosphoryl lipid A (MPLA), imiquimod (R-837), resiquimod (R-848), poly(I:C), and heat killed Listeria monocytogenes.ResultsR-848 proved to be the most suitable Toll-like receptor agonist for our novel immunotherapeutic approach. In combination with covalently bound mannan, R-848 significantly reduced tumor growth. Adding poly(I:C) and L. monocytogenes resulted in complete recovery in 83% of mice and in their protection from the re-transplantation of melanoma cells.ConclusionAn efficient cancer treatment results from the combination of Toll-like receptor agonists and phagocytosis stimulating ligands bound to the tumor cells.

【 授权许可】

CC BY   
© The Author(s). 2016