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    Home > Active Ingredient News > Digestive System Information > Science sub-journal: Modifying bacteria to express tetanus toxin saves deadly pancreatic cancer

    Science sub-journal: Modifying bacteria to express tetanus toxin saves deadly pancreatic cancer

    • Last Update: 2022-04-28
    • Source: Internet
    • Author: User
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    Written by | Edited by Wang Cong | Typeset by Wang Duoyu | Shui Chengwen Pancreatic Cancer is a malignant gastrointestinal cancer with a high degree of malignancy, which is difficult to diagnose and treat
    .

    In recent years, the incidence and mortality of pancreatic cancer have increased significantly.
    The early diagnosis rate of pancreatic cancer is not high, and it is often found at an advanced stage.
    At this time, the cancer cells have spread and are difficult to treat.
    The 5-year survival rate is less than 7%, which is the best prognosis.
    Poor malignant tumors, so it is also called "the king of cancer"
    .

    Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, accounting for 90% of pancreatic cancers
    .

    According to the latest WHO data, pancreatic cancer is the seventh most common cancer in China in 2020 (an estimated 120,000 new cancers in 2020) and the sixth most fatal cancer (an estimated 120,000 deaths in 2020)
    .

    Immune checkpoint inhibitors have shown excellent results in many cancers, and have even changed the cancer treatment landscape, but this treatment has done little for pancreatic cancer patients
    .

    One reason is that pancreatic cancer is a so-called "cold tumor" that the immune system cannot target and destroy
    .

    Recently, researchers from the Einstein College of Medicine in the United States published a research paper entitled: Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice in Science Translational Medicine, a sub-journal of Science
    .

    The research team developed a new therapeutic strategy to infect mice with pancreatic cancer using genetically engineered Listeria bacteria that express tetanus toxin.
    These Listeria bacteria persist in tumor tissue and are cleared by healthy tissue, thereby activating T cells kill tumors, and when combined with chemotherapy drugs such as gemcitabine, can quickly clear pancreatic cancer cells and reduce cancer metastasis by 87%, and greatly extend lifespan
    .

    Using the tetanus vaccine The vast majority of people are vaccinated against tetanus as a child to prevent diseases caused by tetanus bacillus infection
    .

    The specific memory T cells induced by tetanus toxoid circulate lifelong in the blood, and people who receive this vaccine will develop a strong immune response if they are later exposed to the tetanus toxin produced by tetanus bacteria
    .

    The research team used the same tetanus vaccine as humans to inoculate mice with pancreatic cancer, and then integrated the gene encoding the tetanus toxin into non-pathogenic Listeria, a bacterium that can rapidly infect human cells and colonize tissues.
    spread
    .

    The team then injected the engineered listeria into pancreatic cancer model mice that had previously been vaccinated against tetanus
    .

    Dr.
    Gravekamp and her colleagues effectively elicited a potent and specific immune response against pancreatic cancer cells by infecting them with bacteria that deliver tetanus toxin into the cells
    .

    Listeria exploiting the suppressive environment of cancer is actually very weak and easily killed by the immune systems of humans and animals, except in the tumor microenvironment
    .

    So this therapeutic strategy actually takes advantage of the suppressive tumor microenvironment of pancreatic cancer, where these Listeria bacteria can survive for a long time in the tumor area of ​​pancreatic cancer, whereas in healthy tissue, these Listeria bacteria are quickly attacked by the immune system.
    clear
    .

    Once these engineered Listeria bacteria infect tumor cells, their tetanus toxin gene expresses tetanus toxin in the tumor tissue, inducing a strong immune response
    .

    Tetanus toxin activates tetanus-specific memory T cells that were pre-existing from tetanus vaccination, and activates CD4 T cells to attack and kill cancer cells
    .

    T cell responses can be further enhanced by adding low doses of gemcitabine, a chemotherapy drug that lowers immunosuppression
    .

    The treatment reduced the size of pancreatic tumors in mice by an average of 80 percent, reduced cancer metastasis by 87 percent, and lived 40 percent longer in treated mice than in untreated mice
    .

    In addition, the team said the treatment could also be used to treat other types of cancer besides pancreatic cancer, such as ovarian cancer, for which current immunotherapies do not respond well
    .

    It is reported that this research has been licensed to Loki Therapeutics for subsequent commercial development, and the corresponding author of the paper, Professor Claudia Gravekamp, ​​is also the co-founder and chief scientist of Loki Therapeutics
    .

    Link to the paper: https:// Open for reprinting.
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