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  1. Article ; Online: The Molecular Imaging of Natural Killer Cells

    Mariya Shapovalova / Sean R. Pyper MD, PhD / Branden S. Moriarity PhD / Aaron M. LeBeau PhD

    Molecular Imaging, Vol

    2018  Volume 17

    Abstract: The recent success of autologous T cell-based therapies in hematological malignancies has spurred interest in applying similar immunotherapy strategies to the treatment of solid tumors. Identified nearly 4 decades ago, natural killer (NK) cells represent ...

    Abstract The recent success of autologous T cell-based therapies in hematological malignancies has spurred interest in applying similar immunotherapy strategies to the treatment of solid tumors. Identified nearly 4 decades ago, natural killer (NK) cells represent an arguably better cell type for immunotherapy development. Natural killer cells are cytotoxic lymphocytes that mediate the direct killing of transformed cells with reduced or absent major histocompatibility complex (MHC) and are the effector cells in antibody-dependent cell-mediated cytotoxicity. Unlike T cells, they do not require human leukocyte antigen (HLA) matching allowing for the adoptive transfer of allogeneic NK cells in the clinic. The development of NK cell-based therapies for solid tumors is complicated by the presence of an immunosuppressive tumor microenvironment that can potentially disarm NK cells rendering them inactive. The molecular imaging of NK cells in vivo will be crucial for the development of new therapies allowing for the immediate assessment of therapeutic response and off-target effects. A number of groups have investigated methods for detecting NK cells by optical, nuclear, and magnetic resonance imaging. In this review, we will provide an overview of the advances made in imaging NK cells in both preclinical and clinical studies.
    Keywords Biology (General) ; QH301-705.5 ; Medical technology ; R855-855.5
    Subject code 610 ; 570
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher Hindawi - SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach

    Shilvi Joshi / Lang Chen / Michael B. Winter / Yi-Lun Lin / Yang Yang / Mariya Shapovalova / Paige M. Smith / Chang Liu / Fang Li / Aaron M. LeBeau

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 11

    Abstract: Abstract The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a ... ...

    Abstract Abstract The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1–P4′ amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.
    Keywords Medicine ; R ; Science ; Q
    Subject code 540
    Language English
    Publishing date 2017-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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