Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT‐II T Cell Activation Conferring Tumor Protection in Mice

Abstract

Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova. T cells from Ova-specific OT-II but not from C57BL/6 or SKH-1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon-gamma production, a known anti-melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova-expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen-presenting cells when compared to their Ova-vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.

Murine Macrophages Modulate Their Inflammatory Profile in Response to Gas Plasma-Inactivated Pancreatic Cancer Cells

“…This and the current work add to important routes for immune-relevant effects of gas plasma treatment of cancer cells. The first is immediate effects by oxidative modifications of target proteins and receptors through gas plasma-derived ROS/RNS [ 55 , 56 ]. This may also affect other targets of the TME, such as thiols [ 57 , 58 , 59 ] and extracellular matrix hyaluron [ 60 ], that upon plasma treatment were recently identified to show disrupted binding to its receptor CD44 [ 61 ].…”

ROS Cocktails as an Adjuvant for Personalized Antitumor Vaccination?

“…In a recent study, we used chicken ovalbumin (Ova) to study the immunogenicity of multi-ROS cocktails in vitro and in vivo [66]. Using transgenic OT-II mice harboring Ova-specific T cells, we found gas plasma modified Ova to elicit significantly enhanced T cell activation compared to native antigen (Ova).…”

Combining Nanotechnology and Gas Plasma as an Emerging Platform for Cancer Therapy: Mechanism and Therapeutic Implication

“…While plasmas generate a mixture of ROS/RNS simultaneously with defined spatiotemporal profiles [ 83 , 84 ], the overall deposition of these redox agents can be controlled either via the treatment time or energy in put [ 85 ]. Once close to biological targets, the ROS/RNS react with different biomolecules and partially oxidize, for instance, proteins [ 86 ], peptides [ 87 ], amino acids [ 88 ], lipids [ 89 ], and nuclei acids [ 90 ]. Accordingly, gas plasma-treated cells are potentially challenged by multiple ways, including diffusion of long-lived ROS such as hydrogen peroxide into the cytosol via aquaporins [ 91 ], lipid peroxidation [ 92 ], uptake of proteins with oxidative posttranslational modifications (PTMs) [ 86 ], and stresses through damage-associated pattern (DAMPs) being released into the microenvironment [ 93 ].…”