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Author: Bekeschus, Sander Ă— End date: 2024 Ă— Start date: 2020 Ă— DDC: 610 Ă— Type: Text Ă— Type: article Ă—

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    Acquired cancer tyrosine kinase inhibitor resistance: ROS as critical determinants
    (London : Macmillan Publishers, part of Springer Nature, 2021) Bekeschus, Sander
    [No abstract available]
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    ROS Cocktails as an Adjuvant for Personalized Antitumor Vaccination?
    (Basel : MDPI, 2021) Clemen, Ramona; Bekeschus, Sander
    Cancer is the second leading cause of death worldwide. Today, the critical role of the immune system in tumor control is undisputed. Checkpoint antibody immunotherapy augments existing antitumor T cell activity with durable clinical responses in many tumor entities. Despite the presence of tumor-associated antigens and neoantigens, many patients have an insufficient repertoires of antitumor T cells. Autologous tumor vaccinations aim at alleviating this defect, but clinical success is modest. Loading tumor material into autologous dendritic cells followed by their laboratory expansion and therapeutic vaccination is promising, both conceptually and clinically. However, this process is laborious, time-consuming, costly, and hence less likely to solve the global cancer crisis. Therefore, it is proposed to re-focus on personalized anticancer vaccinations to enhance the immunogenicity of autologous therapeutic tumor vaccines. Recent work re-established the idea of using the alarming agents of the immune system, oxidative modifications, as an intrinsic adjuvant to broaden the antitumor T cell receptor repertoire in cancer patients. The key novelty is the use of gas plasma, a multi-reactive oxygen and nitrogen species-generating technology, for diversifying oxidative protein modifications in a, so far, unparalleled manner. This significant innovation has been successfully used in proof-of-concept studies and awaits broader recognition and implementation to explore its chances and limitations of providing affordable personalized anticancer vaccines in the future. Such multidisciplinary advance is timely, as the current COVID-19 crisis is inexorably reflecting the utmost importance of innovative and effective vaccinations in modern times.
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    Gas Plasma Protein Oxidation Increases Immunogenicity and Human Antigen-Presenting Cell Maturation and Activation
    (Basel : MDPI, 2022) Clemen, Ramona; Arlt, Kevin; von Woedtke, Thomas; Bekeschus, Sander
    Protein vaccines rely on eliciting immune responses. Inflammation is a prerequisite for immune responses to control infection and cancer but is also associated with disease onset. Reactive oxygen species (ROSs) are central during inflammation and are capable of inducing non-enzymatic oxidative protein modifications (oxMods) associated with chronic disease, which alter the functionality or immunogenicity of proteins that are relevant in cancer immunotherapy. Specifically, antigen-presenting cells (APCs) take up and degrade extracellular native and oxidized proteins to induce adaptive immune responses. However, it is less clear how oxMods alter the protein’s immunogenicity, especially in inflammation-related short-lived reactive species. Gas plasma technology simultaneously generates a multitude of ROSs to modify protein antigens in a targeted and controlled manner to study the immunogenicity of oxMods. As model proteins relevant to chronic inflammation and cancer, we used gas plasma-treated insulin and CXCL8. We added those native or oxidized proteins to human THP-1 monocytes or primary monocyte-derived cells (moDCs). Both oxidized proteins caused concentration-independent maturation phenotype alterations in moDCs and THP-1 cells concerning surface marker expression and chemokine and cytokine secretion profiles. Interestingly, concentration-matched H2O2-treated proteins did not recapitulate the effects of gas plasma, suggesting sufficiently short diffusion distances for the short-lived reactive species to modify proteins. Our data provide evidence of dendric cell maturation and activation upon exposure to gas plasma- but not H2O2-modified model proteins. The biological consequences of these findings need to be elucidated in future inflammation and cancer disease models.