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Dendritic Cell Immunotherapy Gets a Boost

Jul 25, 2016 1:00:30 PM / by Steffen Porwollik

St. John’s wort – a plant of many uses. Hypericin, found in the secretory dark glands of the plant, causes immunogenic cell death (ICD) when photoactivated. Glioma cells undergoing hypericin-induced ICD are used in a new dendritic cell immunotherapy that can prevent and cure high grade gliomas. Image Source: Wikimedia.A new strategy significantly increases the efficacy of dendritic cell immunotherapy against high grade glioma, a severe type of brain cancer. The key: pre-exposing the therapy to glioma cells undergoing immunogenic cell death.

High grade glioma (HGG) is a malignant brain cancer that is characterized by tumorous growth of glial cells, non-neural cells surrounding the neurons of the central and peripheral nervous system. HGG is accompanied by a heartbreakingly poor prognosis and the current lack of a cure. Hundreds of children are diagnosed every year with HGG in Europe and North America.

In the past two decades, dendritic cell immunotherapy gained much traction in the battle against various cancers including HGG. This therapeutic approach is based on stimulation of anti-tumor cytotoxic T cells by dendritic cells that have been “activated” by exposure to tumor-specific antigens. However, oftentimes the activated dendritic cells are just not able to galvanize sufficient numbers of tumor-specific cytotoxic T cells to yield a cure. One approach that seeks to overcome this obstacle uses artificial antigen-presenting cells (as we recently reported). In an alternative strategy, scientists in Leuven, Belgium, reasoned that exposing therapeutic dendritic cells to cancer cells undergoing immunogenic cell death (ICD) could be just the ticket. The results of their efforts, recently published in Science Translational Medicine, [1] proved them right.

The researchers used a known strategy to cause ICD of ex vivo cancer cells – photodynamic therapy with hypericin, a compound found in St John’s wort. Hypericin is a powerful photo-oxidizing molecule that causes cancer cells to undergo apoptosis. Importantly, these dying cells release an abundance of damage-associated molecular patterns (DAMPs) that elicit activated dendritic cells which in turn can facilitate proliferation of cytotoxic T cells.

In their work, the scientists activated murine dendritic cells by incubating them with glioma cells undergoing hypericin-induced ICD. The researchers then tested whether C57BL/6 mice resisted an orthotopic challenge with live glioma cells. They found that mice vaccinated with the dendritic cell immunotherapy showed significantly higher median survival times than non-immunized animals. Furthermore, the scientists wondered which DAMPs were necessary to induce this protective effect, and showed that a protein called HMGB1 (high mobility group box 1) was the most potent DAMP.

But what about curing existing gliomas with this approach? This had never before been achieved with any therapy. The dendritic cell immunotherapy, when combined with standard chemotherapy, not only lengthened the median survival time of HGG mice by over 300% compared to untreated animals, it also completely cured 50% of the animals from HGG! (Drumroll, please.) Remarkably, the dendritic cell immunotherapy partially overcame the immune system ablation from the chemotherapy and shifted the brain immune contexture from regulatory T cells to immunostimulatory T cells.

Dendritic cells may therefore become essential components of anti-cancer treatment regimens of the future. At HemaCare, we offer fresh or cryopreserved dendritic cell-based products from various sources – do not hesitate to contact us at (877) 397-3087, if any of these are of interest to you!

Reference

[1] Garg AD, Vandenberk L, Koks C, Verschuere T, Boon L, Van Gool SW, et al. Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell–driven rejection of high-grade glioma. Sci Transl Med, 2016; 8 (328): 328ra27.

Topics: glioma, brain cancer, Cancer Immunology, cancer immunotherapy, Cytotoxic T Cells, Dendritic Cells, immunogenic cell death, Innovation, T Cells

Steffen Porwollik

Written by Steffen Porwollik

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