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      Study of immunomodulating effects of Streptococcus pyogenes B-7612 bacteria on cellular and humoral immunity of pets

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          Abstract

          For the first time, a study was conducted of the effect of living bacteria of the Streptococcus pyogenes avirulent strain B-7612, on the cellular and humoral immunity indicators of domestic animals (dogs) with signs of immunodeficiency. Lyophilizates of live bacteria was administered intradermally to dogs according to the scheme of 0,02-0,04 ml. for 25 days with an interval of 5 days. At the beginning of the experiment and for every 5 days, all animals were sampled to determine immunity parameters: the number of formed elements (leukocytes, leukocyte formula), protein, albumin, globulin, phagocytic number, phagocytic index, phagocytic activity, bactericidal activity of blood serum, lysozyme activity of blood serum. Blood was taken using blood collection systems. Streptococcus pyogenes strain B-7612 has been found to stimulate the cellular immunity, resulting in an increase in the total number of leukocytes (granulocytes, monocytes and lymphocytes), activation of neutrophilic phagocytic activity of the blood, with simultaneous growth of phagocytic index and phagocytic number, the activity of humoral factors is activated, which indicates an increase in the natural stability of the immune system. In the blood of experimental animals there were no significant changes in the amount of total protein, albumin and globulins compared with the control.

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          Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses.

          Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.
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            White paper on microbial anti-cancer therapy and prevention

            In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting (‘Microbial Based Cancer Therapy’) at the US National Cancer Institute in the summer of 2017. Here, we define ‘Microbial Therapy’ to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care.
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              Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model.

              This study addressed the potential of bacteriolytic therapy using Streptococcus pyogenes in a syngeneic pancreatic carcinoma mouse model. Panc02 tumours were either infected with S pyogenes or were treated with the equivalent volume of vehicle. In addition to assessment of tumour histology and immunohistochemistry, isolated splenocytes were analysed by flow cytometry. Interferon (IFN) gamma secretion as a reaction of splenocytes against tumour cells was shown through the ELISpot technique. A cytotoxic effect of lymphocytes against tumour targets was detected by lactate dehydrogenase (LDH) release. Cytokine levels in serum were measured. A single application of live bacteria into established Panc02 tumours resulted in complete tumour regression. This antitumoral effect was accompanied by massive leucocyte infiltration into the tumours as well as a significant and sustained elevation of systemic levels of the proinflammatory cytokines IFN gamma, tumour necrosis factor alpha and interleukin 6. Lymphocytes obtained from treated mice specifically recognised syngeneic tumour cells in IFN gamma-ELISpot, and most importantly in cellular cytotoxicity assays, indicating a tumour-specific immune response. We provide data that both the direct lytic activity of S pyogenes towards tumour cells and the infection-driven infiltration of tumours by cells of the innate immune system lead to damage of tumour cells followed by a dissemination of tumour components. This last outcome allows for the activation of tumour-specific effector cells, most probably in draining lymph nodes, promoted by the proinflammatory context. Taken together, these data indicate that the application of live S pyogenes may be a promising new treatment strategy for advanced pancreatic cancer patients that warrants further investigation.
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                Author and article information

                Journal
                BIO Web of Conferences
                BIO Web Conf.
                EDP Sciences
                2117-4458
                2024
                July 12 2024
                2024
                : 118
                : 01022
                Article
                10.1051/bioconf/202411801022
                2f2c2c3f-ecbf-49dc-8194-4ac3c0d3cec4
                © 2024

                https://creativecommons.org/licenses/by/4.0/

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