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Prabodhika Mallikaratchy - One of the best experts on this subject based on the ideXlab platform.

  • a homodimeric aptamer variant generated from ligand guided selection activates the t cell receptor Cluster of Differentiation 3 complex
    Molecular therapy. Nucleic acids, 2020
    Co-Authors: Lina Freage, Prabodhika Mallikaratchy, Deana Jamal, Nicole Williams
    Abstract:

    Recently, immunotherapeutic modalities with engineered cells and monoclonal antibodies have been effective in treating several malignancies. Nucleic acid aptamers can serve as alternative molecules to design immunotherapeutic agents with high functional diversity. Here we report a synthetic prototype consisting of DNA aptamers that can activate the T cell receptor Cluster of Differentiation 3 (TCR-CD3) complex in cultured T cells. We show that the activation potential is similar to that of a monoclonal antibody (mAb) against TCR-CD3, suggesting potential for aptamers in developing efficacious synthetic immunomodulators. The synthetic prototype of anti-TCR-CD3e, as described here, was designed using aptamer ZUCH-1 against TCR-CD3e, generated by ligand-guided selection (LIGS). Aptamer ZUCH-1 was truncated and modified with nuclease-resistant RNA analogs to enhance stability. Several dimeric analogs with truncated and modified variants were designed with variable linker lengths to investigate the activation potential of each construct. Among them, a dimeric aptamer with dimensions approximately similar to those of an antibody showed the highest T cell activation, suggesting the importance of optimizing linker lengths in engineering functional aptamers. The observed activation potential of dimeric aptamers shows the vast potential of aptamers in designing synthetically versatile immunomodulators with tunable pharmacokinetic properties, expanding immunotherapeutic designs by using nucleic acid-based ligands such as aptamers.

  • a homodimeric aptamer variant generated from ligand guided selection activates t cell receptor Cluster of Differentiation three complex
    bioRxiv, 2020
    Co-Authors: Lina Freage, Deana Jamal, Nicole Williamns, Prabodhika Mallikaratchy
    Abstract:

    Recently, immunotherapeutic modalities with engineered cells and monoclonal antibodies have been effective in treating several malignancies. However, growing evidence suggests that immune-related adverse events (irAE) lead to severe and long-term side effects. Most iRAEs involve prolonged circulation of antibodies. To address this problem, nucleic acid aptamers can serve as alternative molecules to design immunotherapeutics with high functional diversity and predictable circulation times. Here, we report the first synthetic prototype consisting of DNA aptamers, which can activate T-cell receptor Cluster of Differentiation 3 (TCR-CD3) complex in cultured T-cells. We show that activation potential is similar to that of a monoclonal antibody (mAb) against TCR-CD3, suggesting the potential of aptamers in developing efficacious synthetic immunomodulators. The synthetic prototype of anti-TCR-CD3e, as described herein, was designed using aptamer ZUCH-1 against TCR-CD3e, generated by Ligand Guided Selection (LIGS). Aptamer ZUCH-1 was truncated and modified with nuclease-resistant RNA analogs to enhance stability. Several dimeric analogs with truncated and modified variants were designed with variable linker lengths to investigate the activation potential of each construct. Among them, dimeric aptamer with approximate dimensions similar to those of an antibody showed the highest T-cell-activation, suggesting the importance of optimizing linker lengths in engineering functional aptamers. The observed activation potential of dimeric aptamers shows the vast potential of aptamers in designing synthetically versatile immunomodulators with tunable pharmacokinetic properties, expanding immunotherapeutic designs with the use of nucleic acid-based ligands such as aptamers.

  • Ligand-guided selection of aptamers against T-cell Receptor-Cluster of Differentiation 3 (TCR-CD3) expressed on Jurkat.E6 cells.
    Analytical Biochemistry, 2016
    Co-Authors: Hasan E. Zumrut, George E. Maio, Sana Batool, Prabodhika Mallikaratchy
    Abstract:

    Abstract We recently introduced a screening technology termed li gand- g uided s election, (LIGS), to selectively identify target-specific aptamers from an evolved cell-SELEX library. Cell-SELEX utilizes a large combinatorial single-stranded oligonucleotide library and progressively selects DNA ligands against whole cells with variable DNA-binding affinities and specificities by repeated rounds of partition and amplification. LIGS exploits the partition step and introduces a secondary, pre-existing high-affinity monoclonal antibody (mAb) ligand to outcompete and elute specific aptamers towards the binding target of the antibody, not the cell. Here, using anti-CD3e mAb against the Cluster of Differentiation 3 (CD3e), as the guiding ligand against one of the domains of the T-cell Receptor (TCR) complex expressed on Jurkat.E6 cells, we discovered three specific aptamers against TCR complex expressed on an immortalized line of human T lymphocyte cells. In sum, we demonstrate that specific aptamers can be identified utilizing an antibody against a single domain of a multidomain protein complex in their endogenous state with neither post- nor pre-SELEX protein manipulation.

Alexander J. Thompson - One of the best experts on this subject based on the ideXlab platform.

Takahide Mori - One of the best experts on this subject based on the ideXlab platform.

  • Human endometrial stromal cells and decidual cells express Cluster of Differentiation (CD) 13 antigen/aminopeptidase N and CD10 antigen/neutral endopeptidase.
    Biology of Reproduction, 1992
    Co-Authors: Kimitoshi Imai, Michiyuki Maeda, Hiroshi Fujiwara, Kenji Takakura, Hideharu Kanzaki, Norihiko Okamoto, Masatoshi Kariya, Takahide Mori
    Abstract:

    With specific monoclonal antibodies, we found that human endomethal stromal cells and decidual cells express two functionrelated surface antigens. Indirect immunofluorescence staining revealed that both endometrial stromal cells and decidual cells during the first trimester of pregnancy expressed Cluster of Differentiation (CD) 13 antigen and CD1O antigen, which are identical to aminopeptidase N and neutral endopeptidase, respectively. By flow cytometric analysis, CD1 3 antigen was detected on 8293% of the examined cells, and CD1O antigen was detected on 75-93% of the examined cells in endometrial stromal cellenriched preparations. Furthermore, peptidase activity was detected in these cell preparations by an assay based on the hydrolysis of alanine-p-nitroanilide into p-nitroaniline and alanine.

  • human endometrial stromal cells and decidual cells express Cluster of Differentiation cd 13 antigen aminopeptidase n and cd10 antigen neutral endopeptidase
    Biology of Reproduction, 1992
    Co-Authors: Kimitoshi Imai, Michiyuki Maeda, Hiroshi Fujiwara, Kenji Takakura, Hideharu Kanzaki, Norihiko Okamoto, Masatoshi Kariya, N Emi, Takahide Mori
    Abstract:

    With specific monoclonal antibodies, we found that human endomethal stromal cells and decidual cells express two functionrelated surface antigens. Indirect immunofluorescence staining revealed that both endometrial stromal cells and decidual cells during the first trimester of pregnancy expressed Cluster of Differentiation (CD) 13 antigen and CD1O antigen, which are identical to aminopeptidase N and neutral endopeptidase, respectively. By flow cytometric analysis, CD1 3 antigen was detected on 8293% of the examined cells, and CD1O antigen was detected on 75-93% of the examined cells in endometrial stromal cellenriched preparations. Furthermore, peptidase activity was detected in these cell preparations by an assay based on the hydrolysis of alanine-p-nitroanilide into p-nitroaniline and alanine.

Roy L. Silverstein - One of the best experts on this subject based on the ideXlab platform.

  • Oxidized Lipid Uptake by Scavenger Receptor CD36 (Cluster of Differentiation 36) Modulates Endothelial Surface Properties and May Contribute to Atherogenesis.
    Arteriosclerosis Thrombosis and Vascular Biology, 2017
    Co-Authors: Roy L. Silverstein
    Abstract:

    For many years, vascular biologists and pathologists have known that atherosclerosis is a spatially discontinuous disease; plaque tends to form in specific locations, especially branch points in large arteries, where blood flow is discontinuous and disordered. Furthermore, plaque formation progresses temporally from the proximal arterial tree to more distal vessels. It is also well known that vascular endothelial cells are sensitive to shear stress patterns and blood flow1 and, in fact, express a robust mechanosensory system made up of intracellular signaling pathways that are triggered by integrins, selectins, and cilia.2 Unidirectional flow in straight vessels, such as the distal aorta, is atheroprotective, whereas disordered flow (DF) at curvatures and branch points, such as the aortic arch, promotes inflammatory signaling, endothelial dysfunction, leukocyte recruitment, and plaque formation.3 An article by Le Master et al4 published in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology presents elegant new data that helps integrate these observations into a pathogenic model that relates disordered blood flow to upregulated endothelial cell expression of the scavenger receptor CD36 (Cluster of Differentiation 36), increased uptake of oxidized lipids, and increased endothelial cell stiffness. See accompanying article on page 64 The …

Peter T.-h. Wong - One of the best experts on this subject based on the ideXlab platform.

  • MicroRNAs regulating Cluster of Differentiation 46 (CD46) in cardioembolic and non-cardioembolic stroke.
    PLOS ONE, 2017
    Co-Authors: Fung Lin Yong, Arunmozhiarasi Armugam, Chee Woon Wang, Kandiah Jeyaseelan, Peter T.-h. Wong
    Abstract:

    : Ischemic stroke is a major cause of mortality and morbidity globally. Among the ischemic stroke subtypes, cardioembolic stroke is with poor functional outcome (Modified Rankin score ≥ 2). Early diagnosis of cardioembolic stroke will prove beneficial. This study examined the microRNAs targeting Cluster of Differentiation 46 (CD46), a potential biomarker for cardioembolic stroke. CD46 mRNA level was shown to be differentially expressed (p < 0.001) between cardioembolic stroke (median = 1.32) and non-cardioembolic stroke subtypes (large artery stroke median = 5.05; small vessel stroke median = 6.45). Bioinformatic search showed that miR-19a, -20a, -185 and -374b were found to target CD46 mRNA and further verified by luciferase reporter assay. The levels of miRNAs targeting CD46 were significantly reduced (p < 0.05) in non-cardioembolic stroke patients (large artery stroke median: miR-19a = 0.63, miR-20a = 0.42, miR-185 = 0.32, miR-374b = 0.27; small artery stroke median: miR-19a = 0.07, miR-20a = 0.06, miR-185 = 0.07, miR-374b = 0.05) as compared to cardioembolic stroke patients (median: miR-19a = 2.69, miR-20a = 1.36, miR-185 = 1.05, miR-374b = 1.23). ROC curve showed that the miRNAs could distinguish cardioembolic stroke from non-cardioembolic stroke with better AUC value as compared to CD46. Endogenous expression of CD46 in Human Umbilical Vein Endothelial Cells (HUVECs) were found to be regulated by miR-19a and miR-20a. Thus implicating that miR-19a and -20a may play a role in pathogenesis of cardioembolic stroke, possibly via the endothelial cells.