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  1. Article ; Online: Critical care utilisation for patients receiving chimeric antigen receptor (CAR) T cell therapy in the UK.

    Pirani, Tasneem / Wilson, Anthony / Brealey, David / Low, Ryan / O'Neill, Suzanne / Le, Jenny / Jhanji, Shaman / Bangash, Mansoor N / Mathew, Amrith / Wright, Christopher / Latif, Anne-Louise / Irvine, David / Kasipandian, Vidya / Singh, Neeraj / Saha, Rohit / Metaxa, Victoria

    British journal of anaesthesia

    2024  Volume 132, Issue 5, Page(s) 1004–1006

    MeSH term(s) Humans ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Patients ; Cell- and Tissue-Based Therapy ; United Kingdom
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2024-03-22
    Publishing country England
    Document type Letter
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1016/j.bja.2024.01.047
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uk I Zs.80: Show issues Location:
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  2. Article: Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons.

    Truex, Nicholas L / Mohapatra, Somesh / Melo, Mariane / Rodriguez, Jacob / Li, Na / Abraham, Wuhbet / Sementa, Deborah / Touti, Faycal / Keskin, Derin B / Wu, Catherine J / Irvine, Darrell J / Gómez-Bombarelli, Rafael / Pentelute, Bradley L

    ACS central science

    2024  Volume 10, Issue 4, Page(s) 793–802

    Abstract: ... T cell responses against cancer and pathogens, but insufficient processing often limits the quantity ... to incorporate proteasomal degradation signals into vaccine designs will lead to enhanced cytotoxic T cell ...

    Abstract Antigen processing is critical for therapeutic vaccines to generate epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often limits the quantity of epitopes released. We address this challenge using machine learning to ascribe a proteasomal degradation score to epitope sequences. Epitopes with varying scores were translocated into cells using nontoxic anthrax proteins. Epitopes with a low score show pronounced immunogenicity due to antigen processing, but epitopes with a high score show limited immunogenicity. This work sheds light on the sequence-activity relationships between proteasomal degradation and epitope immunogenicity. We anticipate that future efforts to incorporate proteasomal degradation signals into vaccine designs will lead to enhanced cytotoxic T cell priming by these vaccines in clinical settings.
    Language English
    Publishing date 2024-03-06
    Publishing country United States
    Document type Journal Article
    ISSN 2374-7943
    ISSN 2374-7943
    DOI 10.1021/acscentsci.3c01544
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: WASP facilitates tumor mechanosensitivity in T lymphocytes.

    Mandal, Srishti / Melo, Mariane / Gordiichuk, Pavlo / Acharya, Sayanti / Poh, Yeh-Chuin / Li, Na / Aung, Aereas / Dane, Eric L / Irvine, Darrell J / Kumari, Sudha

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Cytotoxic T lymphocytes (CTLs) carry out immunosurveillance by scanning target cells of diverse ... physical properties for the presence of antigens. While the recognition of cognate antigen by the T cell receptor is ... of target cells plays an important role in antigen-triggered T cell responses. However, the molecular ...

    Abstract Cytotoxic T lymphocytes (CTLs) carry out immunosurveillance by scanning target cells of diverse physical properties for the presence of antigens. While the recognition of cognate antigen by the T cell receptor is the primary signal for CTL activation, it has become increasingly clear that the mechanical stiffness of target cells plays an important role in antigen-triggered T cell responses. However, the molecular machinery within CTLs that transduces the mechanical information of tumor cells remains unclear. We find that CTL's mechanosensitive ability requires the activity of the actin-organizing protein Wiskott-Aldrich Syndrome Protein (WASP). WASP activation is modulated by the mechanical properties of antigen-presenting contexts across a wide range of target cell stiffnesses and activated WASP then mediates mechanosensitive activation of early TCR signaling markers in the CTL. Our results provide a molecular link between antigen mechanosensing and CTL immune response and suggest that CTL-intrinsic cytoskeletal organizing principles enable the processing of mechanical information from diverse target cells.
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.02.560434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Directed evolution-based discovery of ligands for in vivo restimulation of CAR-T cells.

    Ma, Leyuan / Ramasubramanian, Ranjani / Mehta, Naveen K / Cossette, Benjamin / Morgan, Duncan M / Sukaj, Ina / Bergaggio, Elisa / Kadauke, Stephan / Myers, Regina M / Paruzzo, Luca / Ghilardi, Guido / Grzywa, Tomasz M / Cozzone, Austin / Schuster, Stephen J / Frey, Noelle / Zhang, Libin / Yousefpour, Parisa / Abraham, Wuhbet / Suh, Heikyung /
    Ruella, Marco / Grupp, Stephan A / Chiarle, Roberto / Wittrup, K Dane / Irvine, Darrell J

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Chimeric antigen receptor (CAR) T cell therapy targeting CD19 elicits remarkable clinical efficacy ... of CAR-T cells. We recently reported a strategy to potently restimulate CAR-T cells ...

    Abstract Chimeric antigen receptor (CAR) T cell therapy targeting CD19 elicits remarkable clinical efficacy in B-cell malignancies, but many patients relapse due to failed expansion and/or progressive loss of CAR-T cells. We recently reported a strategy to potently restimulate CAR-T cells
    Language English
    Publishing date 2024-04-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.16.589780
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR.

    Zhang, Angela Q / Hostetler, Alexander / Chen, Laura E / Mukkamala, Vainavi / Abraham, Wuhbet / Padilla, Lucia T / Wolff, Alexandra N / Maiorino, Laura / Backlund, Coralie M / Aung, Aereas / Melo, Mariane / Li, Na / Wu, Shengwei / Irvine, Darrell J

    Nature biomedical engineering

    2023  Volume 7, Issue 9, Page(s) 1113–1128

    Abstract: The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is ... expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T ... tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours ...

    Abstract The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cells with a CAR specific for fluorescein isothiocyanate (FITC) can be directed against solid tumours via the intratumoural administration of a FITC-conjugated lipid-poly(ethylene)-glycol amphiphile that inserts itself into cell membranes. In syngeneic and human tumour xenografts in mice, 'amphiphile tagging' of tumour cells drove tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours. In syngeneic tumours, the therapy induced the infiltration of host T cells, elicited endogenous tumour-specific T cell priming and led to activity against distal untreated tumours and to protection against tumour rechallenge. Membrane-inserting ligands for specific CARs may facilitate the development of adoptive cell therapies that work independently of antigen expression and of tissue of origin.
    MeSH term(s) Humans ; Mice ; Animals ; Fluorescein-5-isothiocyanate/metabolism ; Ligands ; Neoplasms ; T-Lymphocytes ; Immunotherapy, Adoptive
    Chemical Substances Fluorescein-5-isothiocyanate (I223NX31W9) ; Ligands
    Language English
    Publishing date 2023-06-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2157-846X
    ISSN (online) 2157-846X
    DOI 10.1038/s41551-023-01048-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Improved COVID-19 outcomes in CAR-T patients in the age of vaccination and preemptive pharmacotherapeutics.

    Cheok, Kathleen P L / Kirkwood, Amy A / Creasey, Thomas / Tholouli, Eleni / Chaganti, Sridhar / Mathew, Amrith / Dulobdas, Vaishali / Irvine, David / Besley, Caroline / Neil, Lorna / Lown, Robert / Menne, Tobias / Townsend, William / Kuhnl, Andrea / O'Reilly, Maeve / Sanderson, Robin / Sanchez, Emilie / Roddie, Claire

    Leukemia & lymphoma

    2023  Volume 64, Issue 12, Page(s) 2037–2041

    MeSH term(s) Humans ; Receptors, Chimeric Antigen ; COVID-19/prevention & control ; Vaccination ; Immunotherapy, Adoptive
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2023-08-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2023.2248329
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2997: Show issues Location:
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  7. Article ; Online: ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells.

    Bergaggio, Elisa / Tai, Wei-Tien / Aroldi, Andrea / Mecca, Carmen / Landoni, Elisa / Nüesch, Manuel / Mota, Ines / Metovic, Jasna / Molinaro, Luca / Ma, Leyuan / Alvarado, Diego / Ambrogio, Chiara / Voena, Claudia / Blasco, Rafael B / Li, Tongqing / Klein, Daryl / Irvine, Darrell J / Papotti, Mauro / Savoldo, Barbara /
    Dotti, Gianpietro / Chiarle, Roberto

    Cancer cell

    2023  Volume 41, Issue 12, Page(s) 2100–2116.e10

    Abstract: ... antigen receptor (CAR) T cells in hematologic malignancies and solid tumors. The anaplastic lymphoma kinase (ALK ... the development of ALK.CAR-T cells that show potent efficacy in monotherapy against neuroblastoma with high ALK ... specifically potentiates ALK.CAR-T cells but not GD2.CAR-T cells. Mechanistically, ALK inhibitors impair tumor ...

    Abstract Selection of the best tumor antigen is critical for the therapeutic success of chimeric antigen receptor (CAR) T cells in hematologic malignancies and solid tumors. The anaplastic lymphoma kinase (ALK) receptor is expressed by most neuroblastomas while virtually absent in most normal tissues. ALK is an oncogenic driver in neuroblastoma and ALK inhibitors show promising clinical activity. Here, we describe the development of ALK.CAR-T cells that show potent efficacy in monotherapy against neuroblastoma with high ALK expression without toxicity. For neuroblastoma with low ALK expression, combination with ALK inhibitors specifically potentiates ALK.CAR-T cells but not GD2.CAR-T cells. Mechanistically, ALK inhibitors impair tumor growth and upregulate the expression of ALK, thereby facilitating the activity of ALK.CAR-T cells against neuroblastoma. Thus, while neither ALK inhibitors nor ALK.CAR-T cells will likely be sufficient as monotherapy in neuroblastoma with low ALK density, their combination specifically enhances therapeutic efficacy.
    MeSH term(s) Humans ; Anaplastic Lymphoma Kinase/genetics ; Anaplastic Lymphoma Kinase/metabolism ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Antigens, Neoplasm ; T-Lymphocytes ; Cell Line, Tumor
    Chemical Substances Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; Protein Kinase Inhibitors ; Antigens, Neoplasm
    Language English
    Publishing date 2023-11-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2023.11.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5650: Show issues Location:
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    Zs.MG 104: Show issues

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  8. Article: Design of Cytotoxic T Cell Epitopes by Machine Learning of Human Degrons.

    Truex, Nicholas L / Mohapatra, Somesh / Melo, Mariane / Rodriguez, Jacob / Li, Na / Abraham, Wuhbet / Sementa, Deborah / Touti, Faycal / Keskin, Derin B / Wu, Catherine J / Irvine, Darrell J / Gómez-Bombarelli, Rafael / Pentelute, Bradley L

    bioRxiv : the preprint server for biology

    2023  

    Abstract: ... for T cell recognition. Therapeutic vaccines aim to harness these epitopes for priming cytotoxic T cell ...

    Abstract Antigen processing is critical for producing epitope peptides that are presented by HLA molecules for T cell recognition. Therapeutic vaccines aim to harness these epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often reduces vaccine efficacy through limiting the quantity of epitopes released. Here, we set out to improve antigen processing by harnessing protein degradation signals called degrons from the ubiquitin-proteasome system. We used machine learning to generate a computational model that ascribes a proteasomal degradation score between 0 and 100. Epitope peptides with varying degron activities were synthesized and translocated into cells using nontoxic anthrax proteins: protective antigen (PA) and the N-terminus of lethal factor (LF
    Language English
    Publishing date 2023-09-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.22.554289
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Exogenous tetracosahexaenoic acid modifies the fatty acid composition of human primary T lymphocytes and Jurkat T cell leukemia cells contingent on cell type.

    Irvine, Nicola A / West, Annette L / Von Gerichten, Johanna / Miles, Elizabeth A / Lillycrop, Karen A / Calder, Philip C / Fielding, Barbara A / Burdge, Graham C

    Lipids

    2023  Volume 58, Issue 4, Page(s) 185–196

    Abstract: Tetracosahexaenoic acid (24:6ω-3) is an intermediate in the conversion of 18:3ω-3 to 22:6ω-3 in mammals. There is limited information about whether cells can assimilate and metabolize exogenous 24:6ω-3. This study compared the effect of incubation with ... ...

    Abstract Tetracosahexaenoic acid (24:6ω-3) is an intermediate in the conversion of 18:3ω-3 to 22:6ω-3 in mammals. There is limited information about whether cells can assimilate and metabolize exogenous 24:6ω-3. This study compared the effect of incubation with 24:6ω-3 on the fatty acid composition of two related cell types, primary CD3
    MeSH term(s) Animals ; Humans ; Fatty Acids/pharmacology ; Fatty Acids/metabolism ; Jurkat Cells ; Docosahexaenoic Acids/pharmacology ; Leukemia, T-Cell ; Mammals
    Chemical Substances Fatty Acids ; tetracosahexaenoic acid (81247-23-6) ; Docosahexaenoic Acids (25167-62-8)
    Language English
    Publishing date 2023-05-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 241539-2
    ISSN 1558-9307 ; 0024-4201
    ISSN (online) 1558-9307
    ISSN 0024-4201
    DOI 10.1002/lipd.12372
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    Zs.A 645: Show issues Location:
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  10. Article ; Online: Identification of Highly Cross-Reactive Mimotopes for a Public T Cell Response in Murine Melanoma.

    Grace, Beth E / Backlund, Coralie M / Morgan, Duncan M / Kang, Byong H / Singh, Nishant K / Huisman, Brooke D / Rappazzo, C Garrett / Moynihan, Kelly D / Maiorino, Laura / Dobson, Connor S / Kyung, Taeyoon / Gordon, Khloe S / Holec, Patrick V / Mbah, Overbeck C Takou / Garafola, Daniel / Wu, Shengwei / Love, J Christopher / Wittrup, K Dane / Irvine, Darrell J /
    Birnbaum, Michael E

    Frontiers in immunology

    2022  Volume 13, Page(s) 886683

    Abstract: ... not experienced such benefits. These treatments rely upon reinvigorating specific T cell-antigen ... interactions. However, it is often unknown what antigens are being recognized by T cells or how to potently ...

    Abstract While immune checkpoint blockade results in durable responses for some patients, many others have not experienced such benefits. These treatments rely upon reinvigorating specific T cell-antigen interactions. However, it is often unknown what antigens are being recognized by T cells or how to potently induce antigen-specific responses in a broadly applicable manner. Here, we characterized the CD8
    MeSH term(s) Animals ; Antigens, Neoplasm ; CD8-Positive T-Lymphocytes ; Cross Reactions ; Immunotherapy ; Melanoma/therapy ; Mice
    Chemical Substances Antigens, Neoplasm
    Language English
    Publishing date 2022-06-23
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.886683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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