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    Home > Medical News > Medical Research Articles > New method of cell therapy: Potential therapeutic effect on KRAS mutant solid tumors

    New method of cell therapy: Potential therapeutic effect on KRAS mutant solid tumors

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    Adham Bear, MD, PhD, Mark O'Hara, MD, Gerald P.
    Linette, MD, PhD, Beatriz M.
    carno, PhD, and Robert H.
    Vonderheide, MD, DPhil

    .

    Philadelphia-A new cellular immunotherapy technology developed by researchers at the Abramson Cancer Center at the University of Pennsylvania School of Medicine has shown good anti-tumor activity in the laboratory for the treatment of KRAS mutations that were once considered "unusable drugs" Causes difficult-to-treat cancers, including lungs, colorectal, and pancreas
    .

    This study, published on the Nature Communications website, successfully demonstrated that using human cells, a T-cell receptor (TCR) therapy can be designed to mobilize the immune system to attack mutated KRAS solid tumors and shrink them
    .
    First-in-human preclinical work laid the foundation

    .
    It is now in the planning stage of clinical trials for the treatment of patients with advanced pancreatic cancer.
    Tumor harbors specific KRAS mutations and expresses a specific type of human leukocyte antigen, and establishes recognition or HLA for treatment

    .

    Senior author Dr.
    Beatriz M.
    carno said: "We have shown that it is feasible to target mutations in KRAS immunologically and may be extended to a group of patients with lung, colon, and pancreatic tumors

    .
    " Perelman School of Medicine, University of Pennsylvania ( Perelman School of Medicine at the University of Pennsylvania) Associate Professor of Pathology and Laboratory Medicine, Center for Cell Immunotherapies, Abramson Cancer Center and Parker Institute for Cancer Immunotherapy ( Member of the Parker Institute for Cancer Immunotherapy)

    .
    "We look forward to taking this research to the next level, closer to clinical research

    .
    "

    KRAS mutations are one of the most common mutations observed in cancer and have been shown to drive tumor development and growth
    .
    Until recently, targeted therapies have been shown to be able to successfully treat one of the most common KRAS mutations in lung cancer; however, there are currently no treatments for most of the KRAS mutations that are prevalent in other tumor types

    .
    Immune targeting of mutant KRAS is an alternative treatment method, but research and understanding are less

    .

    Using multi-omics methods, the research team at the University of Pennsylvania identified specific neoantigen karst genes associated with mutations at the G12 site
    .
    Neoantigens are protein fragments formed on the surface of cancer cells when certain mutations occur in tumor DNA

    .
    More than 75% of KRAS protein changes occur in G12, making it an ideal target for treatment

    .

    Armed with this knowledge, the researchers tested specific TCR therapy for Karst G12 mutations and specific HLA types that are highly prevalent in patients
    .
    They showed in mouse tumor models that it can effectively attack and eliminate tumor cells

    .
    Hla is an important part of the immune system because they encode cell surface molecules that provide specific neoantigens to T cell receptors on T cells

    .

    In other words, hla is the key genetic code for these engineered T cells to discover and attack tumors
    .

    This research further supports the use of neoantigens to target tumor cells for cell therapy and cancer vaccines, and is ongoing at the University of Pennsylvania School of Medicine and elsewhere
    .

    Importantly, the new antigen and HLA information from this latest study is being used to develop TCR therapies for the treatment of solid tumors, as well as new cancer vaccines
    .
    Based on these latest findings, the team initiated a clinical trial of a vaccine against pancreatic cancer with mutations in KRAS, led by Mark O'Hara, MD, assistant professor of hematology-oncology at the University of Pennsylvania and co-author of the study

    .

    According to regulatory approval, the first clinical trial of TCR therapy is expected to be launched at the Penn's Abramson Cancer Center as early as 2022 for advanced pancreatic patients suffering from two diseases at the same time.
    Cancer patient
    Karst found mutations and specific HLA types in this latest study, which may represent up to 10% of pancreatic cancer patients
    .
    However, this study opens the door for expanding the patient population, as researchers continue to discover more neoantigens from the region,
    karst genes and other mutated oncogenes involved in driving cancer
    .

    "The evidence we provide shows that this oncoprotein is a very promising clinical target for immunotherapy," said Adham Bear, a lecturer in the Department of Hematology and Oncology at the University of Pennsylvania and a member of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania.
    Said the medical doctor

    .
    "Now that we have identified these new antigens and T cell receptors, our goal is to translate these findings into new therapies at the University of Pennsylvania

    .
    "


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