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    Home > Biochemistry News > Biotechnology News > Anti-cancer breakthrough! More than half of the mice treated with CAR-T were cured.

    Anti-cancer breakthrough! More than half of the mice treated with CAR-T were cured.

    • Last Update: 2020-09-19
    • Source: Internet
    • Author: User
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    On September 2, a team of scientists from hope city in the United States reported in the journal Science Translational Medicine a breakthrough in the successful targeting and eradication of solid tumors in a joint CAR-T and lysovirus therapy.
    in preclinical studies, researchers genetically engineered a lysolytic virus to enter tumor cells and force them to express CD19 proteins on the surface.
    , they then used CAR-T cells targeted at CD19 to identify and attack these solid tumors.
    this innovative combined treatment has completely receded about 60% of mouse tumors, created great hope for CAR-T's use in solid tumor therapy.
    cover story: CAR and Driver - Embedded AntigenSuper (CAR) T-Cells are cancer immunotherapy for identifying specific antigens on the surface of a tumor.
    car-T cell therapy can cause damage to healthy cells and/or cancer cells to escape attack when there is no convenient target tumor antigen to use.
    to solve this problem, Park and others first infected tumors with a solute virus that expressed CD19 antigens and then delivered CD-19-CAR-T cells to destroy them.
    above shows a tumor infected with the lysovirus (green) with a blue nucleus.
    (Source: A. K. PARK, S.-I. KIM, S. J. PRICEMAN/CITY OF HOPE) CAR-T therapy is one of the key pillars of cancer immunotherapy.
    2017, the FDA has approved three CD19 CAR-T therapies for the treatment of certain types of blood cancers, including B-cell lymphoma and acute lymphoblastic leukemia.
    , however, although such treatments have significant effects on blood cancer, little progress has been made in improving the treatment of solid tumors.
    In this new study, Anthony K. Park and others overcome two major challenges that make immunotherapy difficult to treat solid tumors: 1) solid tumors have limited targets for CAR-T cells, most solid tumors lack a clear target, and 2) solid tumors have a "protective wall" around them, a microenvironment of immunosuppressive tumors that makes it difficult for CAR-T cells to survive, amplification, and fight cancer.
    Yuman Fong, from City of Hope, suggests that the virus may be able to break through these barriers.
    team designed a lysate virus, OV19t, that can enter cancer cells and replicate itself using the cell's own mechanisms, while reducing the expression of cancer cells.
    they have succeeded in achieving this in triple-negative breast, pancreatic, prostate, ovarian, head and neck cancer, and brain tumor cells.
    In-body, the lysosovirus effectively delivers CD19t to solid tumors: Figure B shows that after infecting cancer cells with lysovirus, the cancer cells expressed a wealth of CD19 (purple) on their surface (Source: Science Translational Medicine), the researchers tested the "OV19t-CD19-CAR-T" combination therapy in cells from a variety of solid tumors, including pancreatic, prostate and ovarian cancers.
    When infecting tumor cells with OV19t, the researchers observed a positive signal that tumor cells express CD19t much earlier than the virus can kill them, and that the cancer cell surface expresses the new CD19 before the virus mediates tumor cleavage, which provides a window into the tumor cells that use CD19-CAR-T to target the expression CD19t.
    when OV19t was combined with CD19-CAR-T, cancer cells were widely killed.
    , the researchers continued to experiment with this strategy in mouse tumor models.
    they found that combining OV19t with CAR-T cells produced strong synergies that cured more than half of mice, with 60 percent of mice in complete remission and only 22 percent of mice treated with OV19t alone completely receding.
    In immune mouse tumor models, OV19t combined CD19-CAR-T cells for anti-tumor action (Source: Science Scienceal Medicine) Researchers also found that in mice treated with co-treatment, OV19t continued to spread to cancer cells, killing tumor cells to release additional copies of the virus, allowing neighboring tumor cells to express CD19, resulting in significantly stronger tumor cell activity.
    more importantly, when cancer cells were used again to challenge cured mice, no new tumors formed, suggesting that the virus-CAR-T joint program helped build tumor-specific immune memory that prevented cancer from returning.
    CD19-CAR-T cell-mediated tumor killer promotes the release of viral particles and persistent tumor cell infection, Figure A shows the spread of the engineered bovine pox virus (OVm19t, green) in colorectal cancer cells in mice treated with CD19-CAR-T.
    (Source: Science Translational Medicine) In addition to expressing CD19t, studies have also confirmed that the introduction of viruses reverses the harsh micro-environment of tumors, making them more susceptible to CAR-T cell therapy.
    why mice did not respond to the "OV19t-CD19-CAR-T" combined therapy, the researchers speculated that it may have been because the treatment induced PD-L1 expression.
    , they suggest that in the future, potential treatment strategies for blocking drugs can be explored at the "OV19t-CD19-CAR-T" joint checkpoint.
    , the researchers believe the new findings could expand the use of CD19-CAR-T therapy to treat patients with solid tumors.
    " our study shows that lysovirus is a powerful and promising way to strategically target solid tumors by strategically teaming up with CAR-T.
    the most exciting prospect of this new study is that in the future we may be able to apply this strategy to any cancer patient.
    J. Priceman, who led the study, added.
    that the team is working on a clinical trial to test the combination therapy.
    trial will first test the safety of OV19t in solid tumor patients.
    if OV19t is shown to be safe and effective, it can be tested for combination therapy.
    Priceman estimates that the trial will begin in 2022.
    : s1. Anthony K. Park et al. Effective group immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors. Science Translational Medicine (2020). Scientists use two powerful immunotherapies to total solid tumors (Source: City of Hope)
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