• personalized cancer vaccines reality

    From ScienceDaily@1:317/3 to All on Tuesday, March 22, 2022 22:30:46
    personalized cancer vaccines reality
    A novel prioritisation pipeline and `plug-and-play' vaccine technology
    opens up the possibility of rapidly generating tailored cancer vaccines for clinical use

    Date:
    March 22, 2022
    Source:
    eLife
    Summary:
    Scientists have created a pipeline for identifying, prioritizing
    and evaluating potential tumor antigens for the fast generation
    of cancer vaccines, according to a new report.



    FULL STORY ========================================================================== Scientists have created a pipeline for identifying, prioritising and
    evaluating potential tumour antigens for the fast generation of cancer vaccines, according to a report published today in eLife.


    ==========================================================================
    The new approach could help researchers quickly identify tumour-specific antigens recognised by cytotoxic T cells, generating a powerful, durable
    and highly specific response against an individual's tumour. This
    could lead in turn to a quicker and easier way to generate effective, personalised cancer vaccines based on the identified antigens.

    "For a cancer vaccine to be effective, we need to select target antigens
    that elicit a strong immune response, are exclusively present on cancer
    cells and are tailored to an individual's unique tumour type," explains
    first author Sara Feola, Postdoctoral Researcher at the ImmunoViroTherapy
    Lab (IVTLab), University of Helsinki, Finland. "However, only a few,
    if any, of the antigens on a tumour meet those characteristics, making
    it very difficult to identify and prioritise potentially effective
    candidates. Our pipeline comprises all the essential steps for the optimal development of a therapeutic cancer vaccine, but which could be carried
    out much more quickly on an individual patient basis, enabling true personalised therapy." "Developing personalised cancer vaccines needs
    several different technologies working together and working fast," adds
    senior author Vincenzo Cerullo, Professor of Biological Drug Development
    at the University of Helsinki and group leader at IVTLab. "We need fast
    and reliable methods to identify and prioritise antigens, as well as
    rapid, inexpensive and feasible approaches to deliver these antigens
    to patients. During the past six years, we've been working on a project supported by the European Research Council (ERC) to make all the pieces
    of this complex puzzle work together, creating the pipeline that has
    been partially described in this work.

    "Our research, which builds on previous work, involves developing a
    novel approach to identify tumour-specific antigens from very small
    samples, creating a novel algorithm to prioritise peptides based on
    their similarity to pathogen- derived peptides, and building several
    different plug-and-play technologies to deliver these peptides together
    with viruses or bacteria that kill cancer cells." In the current study,
    the team began by investigating the antigen landscape of a tumour cell --
    that is, all the different peptides on the cell surface. They studied a
    mouse model of colon cancer and used state-of-the-art technologies, such
    as an immunopeptidomic approach based on mass spectrometry analysis, to
    explore surface antigens on the cell. This generated a list of thousands
    of peptide candidates and presented a challenge of how to prioritise them.

    The team used two parallel lines of investigation: first, they looked
    at the relative amounts of the peptides on cancer cells compared with
    normal cells.

    This gave them clues as to whether the antigen was truly tumour specific.

    Second, they used a software tool previously developed in their lab to
    identify tumour antigens that are similar to known pathogen antigens, exploiting their potential ability to cause a similar immune response
    to the pathogen antigens.

    Using these methods, the team narrowed their candidate list down from
    thousands to 26 antigen candidates. They then studied the potential
    of these antigens further by testing how well they stimulated T cells,
    and how effectively they bind to an adenoviral vector that would form
    the basis of the vaccine. All the candidate antigen peptides interacted
    with the viral vector, but six peptides performed best and were taken
    forward for further tests.

    The next stage was to see whether a vaccine carrying these target antigens could stimulate enough of an immune response to control or halt tumour
    growth.

    To test this, the team used mice with colon tumours on their left and
    right flanks. They then treated one side of the mice with the vaccine
    coated with each of the candidate peptide antigens. As hoped, they found
    that vaccines carrying the peptides improved anti-tumour growth in the
    treated tumour, but one of the vaccines improved anti-tumor growth in the untreated tumours - - suggesting that the peptide antigen in this vaccine
    had mounted a powerful systemic immune response against the tumours.

    "We have developed and validated a pipeline that covers for the first time
    all the stages of personalised cancer vaccine development, starting with isolating peptides from a primary tumour to analysing them to identify
    the best candidates," Cerullo concludes. "This pipeline is currently
    being validated in human cancer patients under our flagship project on precision cancer medicine, iCAN.

    "Together, our findings demonstrate the feasibility of applying the
    pipeline to generate a tailored cancer vaccine by focusing on the prioritisation and selection criteria and adopting quick plug-and-play technology, called PeptiCRAd, through decorating a clinically approved adenovirus vector with the selected peptides. This opens up the
    possibility of rapidly generating vaccines for clinical use, where
    effective personalised therapies represent a major goal of successful treatment."

    ========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
    for style and length.


    ========================================================================== Journal Reference:
    1. Sara Feola, Jacopo Chiaro, Beatriz Martins, Salvatore Russo, Manlio
    Fusciello, Erkko Ylo"sma"ki, Chiara Bonini, Eliana Ruggiero, Firas
    Hamdan, Michaela Feodoroff, Gabriella Antignani, Tapani Viitala,
    Sari Pesonen, Mikaela Gro"nholm, Rui MM Branca, Janne Lehtio",
    Vincenzo Cerullo. A novel immunopeptidomic-based pipeline for the
    generation of personalized oncolytic cancer vaccines. eLife, 2022;
    11 DOI: 10.7554/ eLife.71156 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220322122552.htm

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