7 research outputs found

    Study of biodegradation of sewage sludge using Vibrio fischeri test

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    Celem pracy było określenie wpływu biodegradacji i wstępnej obróbki fizycznej na toksyczność osadu z oczyszczalni ścieków. Toksyczność była określona za pomocą testu wykorzystującego luminescencyjne bakterie Vibrio fischeri. Najlepszy efekt uzyskano przy zastosowaniu kombinacji wstępnej obróbki fizycznej za pomocą pola elektrostatycznego i biodegradacji za pomocą mieszanych kultur bakterii.The purpose of the work was to determine the effect of biodegradation and initial physical treatment on toxicity of the sewage treatment sludge. Toxicity was determined by mean of the test using luminescent bacteria Vibrio fischeri. The best effect was obtained by application a combination of initial physical treatment using electrostatic fields and biodegradation using mixed cultures of bacteria

    A novel anti-HER2 anthracycline-based antibody-drug conjugate induces adaptive anti-tumor immunity and potentiates PD-1 blockade in breast cancer

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    Abstract Increasing evidence suggests that antibody-drug conjugates (ADCs) can enhance anti-tumor immunity and improve clinical outcome. Here, we elucidate the therapeutic efficacy and immune-mediated mechanisms of a novel HER2-targeting ADC bearing a potent anthracycline derivate as payload (T-PNU) in a human HER2-expressing syngeneic breast cancer model resistant to trastuzumab and ado-trastuzumab emtansine. Mechanistically, the anthracycline component of the novel ADC induced immunogenic cell death leading to exposure and secretion of danger-associated molecular signals. RNA sequencing derived immunogenomic signatures and TCRβ clonotype analysis of tumor-infiltrating lymphocytes revealed a prominent role of the adaptive immune system in the regulation of T-PNU mediated anti-cancer activity. Depletion of CD8 T cells severely reduced T-PNU efficacy, thus confirming the role of cytotoxic T cells as drivers of the T-PNU mediated anti-tumor immune response. Furthermore, T-PNU therapy promoted immunological memory formation in tumor-bearing animals protecting those from tumor rechallenge. Finally, the combination of T-PNU and checkpoint inhibition, such as α-PD1, significantly enhanced tumor eradication following the treatment. In summary, a novel PNU-armed, HER2-targeting ADC elicited long-lasting immune protection in a murine orthotopic breast cancer model resistant to other HER2-directed therapies. Our findings delineate the therapeutic potential of this novel ADC payload and support its clinical development for breast cancer patients and potentially other HER2 expressing malignancies

    Detection of immunogenic cell death and its relevance for cancer therapy

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    Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors

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    The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy

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