Abstract

Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept was accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma technology is tested as a novel anticancer agent. Plasma technology derived ROS diminish tumor growth in vitro and in vivo. Varying the feed gas mixture modifies the composition of ROS. Conditions rich in atomic oxygen correlate with killing activity and elevate intratumoral immune‐infiltrates of CD8+ cytotoxic T‐cells and dendritic cells. T‐cells from secondary lymphoid organs of these mice stimulated with B16 melanoma cells ex vivo show higher activation levels as well. This correlates with immunogenic cancer cell death and higher calreticulin and heat‐shock protein 90 expressions induced by gas plasma treatment in melanoma cells. To test the immunogenicity of gas plasma treated melanoma cells, 50% of mice vaccinated with these cells are protected from tumor growth compared to 1/6 and 5/6 mice negative control (mitomycin C) and positive control (mitoxantrone), respectively. Gas plasma jet technology is concluded to provide immunoprotection against malignant melanoma both in vitro and in vivo.

Highlights

  • Introduction products andreactive oxygen and nitrogen species (ROS) derived from the primary ROS generated by plasmas are more likely to be the biological effectors[8] that may Medical technologies from physics are irreplaceable for both have immunological consequences.[9]diagnosis and therapy of many types of diseases

  • We investigated a novel anticancer treatment modality, medical gas plasma, in a murine syngeneic model of malignant melanoma and tested its ability to promote antitumor efficacy and immuno-stimulation

  • Gas plasma treatment was effective in inactivating melanoma cells in vitro and reducing tumor mass in vivo

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Summary

Plasma Jet Treatment Oxidized and Killed Melanoma Cells by Gas Phase Derived ROS

Medical gas plasma jet technology generates different types of ROS simultaneously (Figure 1a). These ROS were capable of oxidizing murine B16F10 melanoma cells (Figure 1b) to a significant extent when compared to that of untreated cells (Figure 1c). Analyzing the metabolic activity of gas plasma jet treated melanoma cells (Figure 1d), a treatment time dependent decrease was observed that differed significantly from that of the untreated cells (Figure 1e). This decline was associated with terminal cell death (Figure 1f ). Plasma treatment oxidized and subsequently inactivated murine melanoma cells, and the degree of this inactivation was dependent on the feed gas composition and its resulting ROS mixture in the plasma gas phase

Plasma Treatment of Syngeneic Melanoma Reduced Tumor Mass and Increased Leukocyte Tumor Infiltrates In Vivo
Plasma Treatment of Murine Syngeneic Melanomas Increased T-Cell Activation
Gas Plasma Treatment Induced Immunogenic Cancer Cell Death in Melanoma Cells
Vaccination with Plasma-Treated Cells Protected from Melanoma Growth
Discussion
Experimental Section
Conflict of Interest
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