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The paper deals with human cultural stereotypes embedded in mythological consciousness, which have influenced the formation of fear of vaccination against COVID-19. The material was collected in Ukraine in the period from September 2021 to January 2022. By analysing oral narratives and comments from social media users, the authors demonstrate the cultural mechanisms of fear of vaccination, specifically fear of death and fear of metamorphosis, and how they can be overcome. The profusion of memes, anecdotes, and jokes that people read and shared on social media or told each other became a way of overcoming collective fear. Nowadays, not only oral tradition but also social media can constitute a source for studying cultural stereotypes. A folkloristic and culturally anthropological perspective on the fear of vaccination allows us to trace folkloristic phenomena back to our everyday lives and to see folklore as a living, dynamic process that has become part of human culture. © 2022 The Institute of Ethnology of the Czech Academy of Sciences, v.v.i.. All rights reserved.
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Background & Aim: Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) are related side effects of immunotherapies seen in up to 76% of patients treated with CAR-T and 48% of those treated with BiTEs. In up to 27% of the patients, these syndromes may lead to severe consequences. Current treatments for severe CRS are ineffective in >30% of the cases and can worsen ICANS prognosis, calling for novel treatments, especially in light of the expanding use of immunotherapies. Despite their obvious potential, mesenchymal cell (MSC) therapies were seldom investigated in this context. In the present study, Bonus BioGroup has set to assess the potential for treating CRS with MesenCure™, our allogeneic MSC platform, professionalized to enhance the cells’ potency and shown safe and effective in severe COVID patients. Methods, Results & Conclusion: A highly translational and validated CRS model was established in humanized NSG mice bearing human PBMCs, B-cell lymphoma, and CAR-T cells. CAR-T introduction significantly increased the serum levels of proinflammatory cytokines in model animals, indicative of CRS (Fig. 1A). Two IV MesenCure injections were well-tolerated in this model (Fig. 1B) and did not obstruct the CAR-Ts’ ability to inhibit tumor growth by 89% (Fig. 1C, p<0.0001). Remarkably, significant reductions in all proinflammatory cytokines tested (excluding IL-6) were measured in model animals treated with MesenCure, substantiating its potential to treat CRS (Fig. 1A). Interestingly, the magnitudes of these reductions resembled those observed in 50 severe COVID patients treated with MesenCure. MesenCure’s robust immunomodulatory capacity was further demonstrated in vitro by its ability to inhibit the proliferation of activated CD4 T cells with an IC50 of 6k MSC/200k PBMCs, twice more effectively than non-professionalized MSCs. Comparable results were also obtained with CD8 T cells. Similarly, MesenCure inhibited neutrophils’ ROS production by up to 80% within an hour following activation (IC50 19k MSC/200k neutrophils). These effects are likely mediated, in part, by IDO, whose RNA levels were found to be 6.8-fold higher in MesenCure cells than in non-professionalized MSCs (p<0.05), two hours after activation with IFNγ. Moreover, IDO inhibition by 1-MT (1 mM) reduced MesenCure’s (Figure Presented) Fig. 1 (A) The levels of serum proinflammatory cytokines measured in tumor-bearing NSG mice after CRS induction by injection of human PBMCs/CAR-Ts (or saline control) and MesenCure treatment (or saline control). Experimental groups’ designation: Control – not injected with PBMCs/CAR-Ts and not treated by MesenCure;CAR-T – CRS model animals, injected with PBMCs/CAR-Ts but not treated with MesenCure;MesenCure – treated with MesenCure but not injected with PBMCs/CARTs;and CAR-T + MesenCure – CRS model animals treated with MesenCure. (B) Relative change in body weight from the day of tumor induction (Day 0) and (C) IVIS analysis of tumor burden (dorsal aspect) in the above four experimental groups. Statistical significance indicators: ns – not significant, * p<0.05, *** p<0.001, **** p<0.0001. Statistical tests: Holm-Šídák’s multiple comparisons test (A) and two- sided t-test (C). ability to inhibit T cells’ proliferation by 73%. In conclusion, we provide the first evidence for the potential of MSCs and MesenCure, in particular, for treating immunotherapy-related CRS.