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43 results on '"Skeate, Joseph G."'

2. Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies

Author

Skeate, Joseph G., Pomeroy, Emily J., Slipek, Nicholas J., Jones, Bryan J., Wick, Bryce J., Chang, Jae-Woong, Lahr, Walker S., Stelljes, Erin M., Patrinostro, Xiaobai, Barnes, Blake, Zarecki, Trevor, Krueger, Joshua B., Bridge, Jacob E., Robbins, Gabrielle M., McCormick, Madeline D., Leerar, John R., Wenzel, Kari T., Hornberger, Kathlyn M., Walker, Kirsti, Smedley, Dalton, Largaespada, David A., Otto, Neil, Webber, Beau R., and Moriarity, Branden S.

Published
2024
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5. Cas9-induced targeted integration of large DNA payloads in primary human T cells via homology-mediated end-joining DNA repair

Author

Webber, Beau R., primary, Johnson, Matthew J., additional, Skeate, Joseph G., additional, Slipek, Nicholas J., additional, Lahr, Walker S., additional, DeFeo, Anthony P., additional, Mills, Lauren J., additional, Qiu, Xiaohong, additional, Rathmann, Blaine, additional, Diers, Miechaleen D., additional, Wick, Bryce, additional, Henley, Tom, additional, Choudhry, Modassir, additional, Starr, Timothy K., additional, McIvor, R. Scott, additional, and Moriarity, Branden S., additional

Published
2023
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10. Figure S2 from Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929)

Author

Da Silva, Diane M., primary, Enserro, Danielle M., primary, Mayadev, Jyoti S., primary, Skeate, Joseph G., primary, Matsuo, Koji, primary, Pham, Huyen Q., primary, Lankes, Heather A., primary, Moxley, Katherine M., primary, Ghamande, Sharad A., primary, Lin, Yvonne G., primary, Schilder, Russell J., primary, Birrer, Michael J., primary, and Kast, W. Martin, primary

Published
2023
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16. Homology mediated end joining enables efficient non-viral targeted integration of large DNA templates in primary human T cells

Author

Webber, Beau R, primary, Johnson, Matthew J, additional, Slipek, Nicholas S, additional, Lahr, Walker S, additional, DeFeo, Anthony P, additional, Skeate, Joseph G, additional, Qiu, Xiaohong, additional, Rathmann, Blaine, additional, Diers, Miechaleen D, additional, Wick, Bryce, additional, Henley, Tom, additional, Choudhry, Modassir, additional, McIvor, R. Scott, additional, and Moriarity, Branden S, additional

Published
2021
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21. Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929)

Author

Da Silva, Diane M., primary, Enserro, Danielle M., additional, Mayadev, Jyoti S., additional, Skeate, Joseph G., additional, Matsuo, Koji, additional, Pham, Huyen Q., additional, Lankes, Heather A., additional, Moxley, Katherine M., additional, Ghamande, Sharad A., additional, Lin, Yvonne G., additional, Schilder, Russell J., additional, Birrer, Michael J., additional, and Kast, W. Martin, additional

Published
2020
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27. Nanobody–Antigen Conjugates Elicit HPV-Specific Antitumor Immune Responses

Author

Woodham, Andrew W., primary, Cheloha, Ross W., additional, Ling, Jingjing, additional, Rashidian, Mohammad, additional, Kolifrath, Stephen C., additional, Mesyngier, Maia, additional, Duarte, Joao N., additional, Bader, Justin M., additional, Skeate, Joseph G., additional, Da Silva, Diane M., additional, Kast, W. Martin, additional, and Ploegh, Hidde L., additional

Published
2018
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28. Targeted delivery of antigens to CD11b+ cells via nanobodies induces strong antigen-specific T cell and anti-tumor responses

Author

Woodham, Andrew W., primary, Cheloha, Ross W., additional, Ling, Jingjing, additional, Rashidian, Mohammad, additional, Kolifrath, Stephen C., additional, Mesyngier, Maia, additional, Duarte, Joao N., additional, Bader, Justin M., additional, Skeate, Joseph G., additional, Da Silva, Diane M., additional, Kast, W. Martin, additional, and Ploegh, Hidde L., additional

Published
2018
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30. Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression1

Author

Woodham, Andrew W., Raff, Adam B., Raff, Laura M., Da Silva, Diane M., Yan, Lisa, Skeate, Joseph G., Wong, Michael K., Lin, Yvonne G., and Kast, W. Martin

Subjects
Male, Human papillomavirus 16, viruses, Papillomavirus Infections, virus diseases, Oncogene Proteins, Viral, Virus Internalization, female genital diseases and pregnancy complications, Article, Langerhans Cells, Immune Tolerance, Cytokines, Humans, Capsid Proteins, Female, B7-2 Antigen, Peptides, Annexin A2
Abstract

High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.

Published
2014

34. Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection

Author

Skeate, Joseph G., primary, Porras, Tania B., additional, Woodham, Andrew W., additional, Jang, Julie K., additional, Taylor, Julia R., additional, Brand, Heike E., additional, Kelly, Thomas J., additional, Jung, Jae U., additional, Da Silva, Diane M., additional, Yuan, Weiming, additional, and Martin Kast, W., additional

Published
2016
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40. Annexin A2 antibodies but not inhibitors of the annexin A2 heterotetramer impair productive HIV-1 infection of macrophages in vitro

Author

Woodham, Andrew W., Sanna, Adriana M., Taylor, Julia R., Skeate, Joseph G., Da Silva, Diane M., Dekker, Lodewijk V., Kast, W. Martin, Woodham, Andrew W., Sanna, Adriana M., Taylor, Julia R., Skeate, Joseph G., Da Silva, Diane M., Dekker, Lodewijk V., and Kast, W. Martin

Abstract

During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the interaction between A2 and S100A10 were tested for their ability to impair productive HIV-1 infection of macrophages. Our data suggest that interactions between HIV-1 gp120 and A2 exist, though this interaction may be indirect. Furthermore, an anti-A2 antibody impaired HIV-1 particle production in macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote HIV-1 infection of macrophages in its monomeric rather than tetrameric form.

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41. Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.

Author

Bridge J, Johnson MJ, Kim J, Wenthe S, Krueger J, Wick B, Kluesner M, Crane AT, Bell J, Skeate JG, Moriarity BS, and Webber BR

Abstract

Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their lack of alloreactivity, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for ex vivo expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach for ex vivo manufacture of polyclonal, non-virally modified, gene edited chimeric antigen receptor (CAR)-γδ T cells in support of therapeutic application. Engineered CAR-γδ T cells demonstrate high function in vitro and and in vivo . Longitudinal in vivo pharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacy in vivo ., Competing Interests: Competing Interests B.S.M. and B.R.W. have filed patents have been filed relating to the methods and approaches outlined in this manuscript and are founders and hold equity in Luminary Therapeutics who have licensed this IP.

Published
2024
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42. Precision Enhancement of CAR-NK Cells through Non-Viral Engineering and Highly Multiplexed Base Editing.

Author

Wang M, Krueger JB, Gilkey AK, Stelljes EM, Kluesner MG, Pomeroy EJ, Skeate JG, Slipek NJ, Lahr WS, Vázquez PNC, Zhao Y, Eaton EJ, Laoharawee K, Webber BR, and Moriarity BS

Abstract

Natural killer (NK) cells' unique ability to kill transformed cells expressing stress ligands or lacking major histocompatibility complexes (MHC) has prompted their development for immunotherapy. However, NK cells have demonstrated only moderate responses against cancer in clinical trials and likely require advanced genome engineering to reach their full potential as a cancer therapeutic. Multiplex genome editing with CRISPR/Cas9 base editors (BE) has been used to enhance T cell function and has already entered clinical trials but has not been reported in human NK cells. Here, we report the first application of BE in primary NK cells to achieve both loss-of-function and gain-of-function mutations. We observed highly efficient single and multiplex base editing, resulting in significantly enhanced NK cell function. Next, we combined multiplex BE with non-viral TcBuster transposon-based integration to generate IL-15 armored CD19 CAR-NK cells with significantly improved functionality in a highly suppressive model of Burkitt's lymphoma both in vitro and in vivo . The use of concomitant non-viral transposon engineering with multiplex base editing thus represents a highly versatile and efficient platform to generate CAR-NK products for cell-based immunotherapy and affords the flexibility to tailor multiple gene edits to maximize the effectiveness of the therapy for the cancer type being treated., Competing Interests: Conflict of interest statement M.W., E.J.P., M.G.K., B.S.M. and B.R.W. have filed patents covering the methods and approaches outlined in this work.

Published
2024
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43. Long-term lumbar multifidus muscle atrophy changes documented with magnetic resonance imaging: a case series.

Author

Woodham M, Woodham A, Skeate JG, and Freeman M

Subjects
Adult, Follow-Up Studies, Humans, Low Back Pain pathology, Low Back Pain therapy, Male, Muscular Atrophy pathology, Muscular Atrophy therapy, Occupational Diseases therapy, Paraspinal Muscles pathology, Pilot Projects, Recovery of Function, Retrospective Studies, Low Back Pain physiopathology, Magnetic Resonance Imaging, Muscular Atrophy physiopathology, Musculoskeletal Manipulations methods, Occupational Diseases pathology, Occupational Diseases physiopathology, Paraspinal Muscles physiopathology
Abstract

A retrospective case series of three patients with chronic low back pain who received baseline MRI scans revealing multifidus muscle atrophy with fatty replacement is provided. Each patient received spinal manipulative therapy, and two were compliant with low back exercises targeting the multifidus. A follow-up scan performed >1 year later was compared to the baseline scan revealing a decrease in atrophy with fatty replacement in the two patients who performed multifidus-focused low back exercises (15% and 39% on the left and 7% and 32% on the right respectively), and an increase in the patient who underwent spinal manipulation alone (41% and 53%). Interestingly, the decrease in atrophy in the two patients that performed the exercises correlated to functional improvements. Though limited, these results highlight the utility of MRI in quantifying positive and negative long-term changes in multifidus atrophy, which may be an indicator of recovery in chronic low back pain patients.

Published
2014
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