The use of Zymosan A and bacteria anchored to tumor cells for effective cancer immunotherapy: B16-F10 murine melanoma model

Waldmannová, Eva; Caisová, Veronika; Fáberová, Julie; Sváčková, Petra; Kovarova, Marketa; Sváčková, Denisa; Kumžáková, Zuzana; Jačková, Adéla; Vácová, Nikol; Nedbalová, Pavla; Horká, Marie; Kopecký, Jan; Zenka, Jan

doi:10.1016/j.intimp.2016.08.004

Cited by 18 publications

(26 citation statements)

References 37 publications

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“…Previously, we discovered that mannan attached to tumor cells (hydrophobic BAM anchor or SMCC) was a good stimulator of phagocytosis [4, 5]. Thus, we used this finding throughout the present study.…”

Section: Resultsmentioning

confidence: 96%

“…Thus, we used this finding throughout the present study. TLR ligand replacement was necessary due to the previously used LPS, a TLR4 agonist, which poses a dangerous threat to humans [4, 5]. Overall, three different TLR agonists were tested as possible LPS replacements.…”

Section: Resultsmentioning

confidence: 99%

“…Neutrophils were primed according to Dewas et al [13] by the mixture of GM-CSF and TNF-alpha (12 ng and 2.5 ng/ml respectively) for 20 min. The priming solution was enriched with 2 micromolar solution of soluble beta glucan (laminarin) as previously described [5]. Experiments were performed in complement containing medium (FCS was not heat inactivated).…”

Section: Methodsmentioning

confidence: 99%

“…This problem was solved in our previous studies [4, 5], where we described the use of phagocytic receptors agonists anchored to the surface of tumor cells for cancer immunotherapy. To achieve a sufficiently strong therapeutic effect, it was necessary to combine this therapy with simultaneous application of lipopolysaccharide (LPS) – the agonist of TLR4.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore we searched for an effective TLR agonist that would be safe for humans and shows strong synergy with phagocytosis stimulating ligands attached to tumor cells. Anchored mannan was selected for the stimulation of phagocytosis, as it gave the best results (mainly survival prolongation) in previous experiments [4, 5]. Resiquimod (R-848) proved to be the best TLR agonist demonstrating synergy with mannan anchored to tumor cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2982-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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Engineering Controlled Peritumoral Inflammation to Constrain Brain Tumor Growth

Saxena

Lyon

Pai

et al. 2018

Adv Healthcare Materials

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Brain tumors remain a great clinical challenge, in part due to their capacity to invade into eloquent, inoperable regions of the brain. In contrast, inflammation in the central nervous system (CNS) due to injuries activates microglia and astrocytes culminating in an astroglial scar that typically “walls‐off” the injury site. Here, the hypothesis is tested that targeting peritumoral cells surrounding tumors to activate them via an inflammatory stimulus that recapitulates the sequelae of a traumatic CNS injury, could generate an environment that would wall‐off and contain invasive tumors in the brain. Gold nanoparticles coated with inflammatory polypeptides to target stromal cells in close vicinity to glioblastoma (GBM) tumors, in order to activate these cells and stimulate stromal CNS inflammation, are engineered. It is reported that this approach significantly contains tumors in rodent models of GBM relative to control treatments (reduction in tumor volume by over 300% in comparison to controls), by the activation of the innate and adaptive immune response, and by triggering pathways related to cell clustering. Overall, this report outlines an approach to contain invasive tumors that can complement adjuvant interventions for invasive GBM such as radiation and chemotherapy.

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