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  1. Article ; Online: A new way of identifying viral pathogens reactivating in cellular therapy products.

    Cunningham, Anthony L / Micklethwaite, Kenneth

    Immunology and cell biology

    2024  Volume 102, Issue 3, Page(s) 153–155

    Abstract: In this article, we discuss a recently published article that demonstrated a novel way of identifying viral pathogens reactivating in human cells to be used as cellular therapy, in this instance chimeric antigen receptor (CAR) T cells. The authors used ... ...

    Abstract In this article, we discuss a recently published article that demonstrated a novel way of identifying viral pathogens reactivating in human cells to be used as cellular therapy, in this instance chimeric antigen receptor (CAR) T cells. The authors used search engines and databases to identify viruses able to reactivate in T cells and then tested this initially in T-cell cultures, specifically human herpesvirus 6. This virus was then shown to reactivate infrequently in vitro and in vivo in CAR T cells as a consequence of T-cell activation. The methodology may be most clinically useful for more frequently reactivating viruses in other types of cellular therapy such as allogenic CAR T cells or induced pluripotent stem cells.
    MeSH term(s) Humans ; Cell Culture Techniques ; Lymphocyte Activation
    Language English
    Publishing date 2024-01-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12724
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Chimeric antigen receptor T-cell therapy: Prospective observational study of unplanned emergency department presentations.

    Bak, Grace G / Micklethwaite, Kenneth / Maddock, Karen / Coggins, Andrew

    Emergency medicine Australasia : EMA

    2023  Volume 35, Issue 6, Page(s) 1034–1037

    Abstract: Objective: Chimeric antigen receptor T-cell (CAR-T) therapy is an emerging treatment for refractory hematologic malignancy. Unplanned ED presentations following CAR-T present the increasing need for an integrated model of care that allows for the early ... ...

    Abstract Objective: Chimeric antigen receptor T-cell (CAR-T) therapy is an emerging treatment for refractory hematologic malignancy. Unplanned ED presentations following CAR-T present the increasing need for an integrated model of care that allows for the early recognition of its specific complications.
    Methods: This is a prospective observational study at a tertiary centre. CAR-T patients (n = 17) were universally enrolled into a study registry by treating providers. These patients were flagged by investigators to trigger a pop-up notification CAR-T information warning at ED triage. Medical records were reviewed 90 days for unplanned presentations, complications and patient-oriented outcomes.
    Results: Patients receiving CAR-T frequently encountered toxicity within 7 days of therapy. This was typically mild and occurred in an inpatient setting. Medical record review revealed five unplanned ED presentations (that were recognised as post CAR-T) and not directly attributable to specific toxicities.
    Conclusion: If CAR-T therapy is to be used more widely especially in an outpatient model of care, a standardised ED model of care for recognition of specific complications is needed.
    MeSH term(s) Humans ; Cell- and Tissue-Based Therapy ; Hematologic Neoplasms/pathology ; Hematologic Neoplasms/therapy ; Immunotherapy, Adoptive ; Inpatients ; Receptors, Chimeric Antigen ; Prospective Studies
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2023-09-05
    Publishing country Australia
    Document type Observational Study ; Journal Article
    ZDB-ID 2161824-0
    ISSN 1742-6723 ; 1742-6731 ; 1035-6851
    ISSN (online) 1742-6723
    ISSN 1742-6731 ; 1035-6851
    DOI 10.1111/1742-6723.14300
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5940: Show issues Location:
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  3. Article: Chimeric Antigen Receptors for the Tumour Microenvironment.

    Habib, Rosemary / Nagrial, Adnan / Micklethwaite, Kenneth / Gowrishankar, Kavitha

    Advances in experimental medicine and biology

    2020  Volume 1263, Page(s) 117–143

    Abstract: Chimeric antigen receptor T (CAR-T) cell therapy has dramatically revolutionised cancer treatment. The FDA approval of two CAR-T cell products for otherwise incurable refractory B-cell acute lymphoblastic leukaemia (B-ALL) and aggressive B-cell non- ... ...

    Abstract Chimeric antigen receptor T (CAR-T) cell therapy has dramatically revolutionised cancer treatment. The FDA approval of two CAR-T cell products for otherwise incurable refractory B-cell acute lymphoblastic leukaemia (B-ALL) and aggressive B-cell non-Hodgkin lymphoma has established this treatment as an effective immunotherapy option. The race for extending CAR-T therapy for various tumours is well and truly underway. However, response rates in solid organ cancers have been inadequate thus far, partly due to challenges posed by the tumour microenvironment (TME). The TME is a complex structure whose role is to subserve the persistence and proliferation of tumours as well as support their escape from immune surveillance. It presents several obstacles like inhibitory immune checkpoint proteins, immunosuppressive cells, cytokines, chemokines, stromal factors and adverse metabolic pathways. CAR structure and CAR-T therapies have evolved to overcome these obstacles, and we now have several novel CARs with improved anti-tumour activity demonstrated in xenograft models and in some clinical trials. This chapter provides a discussion of the evolution of CAR-T therapies to enable targeting specific aspects of the TME.
    MeSH term(s) Humans ; Immunotherapy, Adoptive ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Chimeric Antigen ; T-Lymphocytes/immunology ; Tumor Microenvironment
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2020-06-25
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-44518-8_8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Donor T cells for CAR T cell therapy.

    Tang, Tiffany C Y / Xu, Ning / Nordon, Robert / Haber, Michelle / Micklethwaite, Kenneth / Dolnikov, Alla

    Biomarker research

    2022  Volume 10, Issue 1, Page(s) 14

    Abstract: Adoptive cell therapy using patient-derived chimeric receptor antigen (CAR) T cells redirected against tumor cells has shown remarkable success in treating hematologic cancers. However, wider accessibility of cellular therapies for all patients is needed. ...

    Abstract Adoptive cell therapy using patient-derived chimeric receptor antigen (CAR) T cells redirected against tumor cells has shown remarkable success in treating hematologic cancers. However, wider accessibility of cellular therapies for all patients is needed. Manufacture of patient-derived CAR T cells is limited by prolonged lymphopenia in heavily pre-treated patients and risk of contamination with tumor cells when isolating T cells from patient blood rich in malignant blasts. Donor T cells provide a good source of immune cells for adoptive immunotherapy and can be used to generate universal off-the-shelf CAR T cells that are readily available for administration into patients as required. Genome editing tools such as TALENs and CRISPR-Cas9 and non-gene editing methods such as short hairpin RNA and blockade of protein expression are currently used to enhance CAR T cell safety and efficacy by abrogating non-specific toxicity in the form of graft versus host disease (GVHD) and preventing CAR T cell rejection by the host.
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2699926-2
    ISSN 2050-7771
    ISSN 2050-7771
    DOI 10.1186/s40364-022-00359-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir

    York, Jarrod / Gowrishankar, Kavitha / Micklethwaite, Kenneth / Palmer, Sarah / Cunningham, Anthony L / Nasr, Najla

    Frontiers in immunology

    2022  Volume 13, Page(s) 873701

    Abstract: Although the advent of ART has significantly reduced the morbidity and mortality associated with HIV infection, the stable pool of HIV in latently infected cells requires lifelong treatment adherence, with the cessation of ART resulting in rapid ... ...

    Abstract Although the advent of ART has significantly reduced the morbidity and mortality associated with HIV infection, the stable pool of HIV in latently infected cells requires lifelong treatment adherence, with the cessation of ART resulting in rapid reactivation of the virus and productive HIV infection. Therefore, these few cells containing replication-competent HIV, known as the latent HIV reservoir, act as the main barrier to immune clearance and HIV cure. While several strategies involving HIV silencing or its reactivation in latently infected cells for elimination by immune responses have been explored, exciting cell based immune therapies involving genetically engineered T cells expressing synthetic chimeric receptors (CAR T cells) are highly appealing and promising. CAR T cells, in contrast to endogenous cytotoxic T cells, can function independently of MHC to target HIV-infected cells, are efficacious and have demonstrated acceptable safety profiles and long-term persistence in peripheral blood. In this review, we present a comprehensive picture of the current efforts to target the HIV latent reservoir, with a focus on CAR T cell therapies. We highlight the current challenges and advances in this field, while discussing the importance of novel CAR designs in the efforts to find a HIV cure.
    MeSH term(s) CD4-Positive T-Lymphocytes ; HIV Infections ; HIV-1 ; Humans ; Immunotherapy, Adoptive ; Virus Latency
    Language English
    Publishing date 2022-04-29
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.873701
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Manipulating the tumor microenvironment by adoptive cell transfer of CAR T-cells.

    Gowrishankar, Kavitha / Birtwistle, Lucy / Micklethwaite, Kenneth

    Mammalian genome : official journal of the International Mammalian Genome Society

    2018  Volume 29, Issue 11-12, Page(s) 739–756

    Abstract: T-cells expressing synthetic chimeric antigen receptors (CARs) have revolutionized immuno-oncology and highlighted the use of adoptive cell transfer, for the treatment of cancer. The phenomenal clinical success obtained in the treatment of hematological ... ...

    Abstract T-cells expressing synthetic chimeric antigen receptors (CARs) have revolutionized immuno-oncology and highlighted the use of adoptive cell transfer, for the treatment of cancer. The phenomenal clinical success obtained in the treatment of hematological malignancies with CAR T-cells has not been reproduced in the treatment of solid tumors, mainly due to the suppressive and hostile tumor microenvironment (TME). This review will address the immunosuppressive features of the TME, which include the stroma, cytokine and chemokine milieu, suppressive regulatory cells and hypoxic conditions, which can all pose formidable barriers for the effective anti-tumor function of CAR T-cells. Some of the novel next generation CARs that have been developed and tested against the TME, will be discussed, to highlight the status of current research in CAR T-cell therapy for solid tumors.
    MeSH term(s) Animals ; Antigens, Neoplasm/immunology ; Humans ; Immunotherapy, Adoptive/methods ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/transplantation ; Tumor Microenvironment/immunology
    Chemical Substances Antigens, Neoplasm ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2018-07-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1058547-3
    ISSN 1432-1777 ; 0938-8990
    ISSN (online) 1432-1777
    ISSN 0938-8990
    DOI 10.1007/s00335-018-9756-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3489: Show issues Location:
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  7. Article: Characterizing piggyBat-a transposase for genetic modification of T cells.

    Sutrave, Gaurav / Xu, Ning / Tang, Tiffany C Y / Dolnikov, Alla / Gloss, Brian / Gottlieb, David J / Micklethwaite, Kenneth P / Gowrishankar, Kavitha

    Molecular therapy. Methods & clinical development

    2022  Volume 25, Page(s) 250–263

    Abstract: Chimeric antigen receptor (CAR) T cells targeting CD19 have demonstrated remarkable efficacy in the treatment of B cell malignancies. Current CAR T cell manufacturing protocols are complex and costly due to their reliance on viral vectors. Non-viral ... ...

    Abstract Chimeric antigen receptor (CAR) T cells targeting CD19 have demonstrated remarkable efficacy in the treatment of B cell malignancies. Current CAR T cell manufacturing protocols are complex and costly due to their reliance on viral vectors. Non-viral systems of genetic modification, such as with transposase and transposon systems, offer a potential streamlined alternative for CAR T cell manufacture and are currently being evaluated in clinical trials. In this study, we utilized the previously described transposase from the little brown bat, designated
    Language English
    Publishing date 2022-03-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2022.03.012
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    Zs.A 7107: Show issues Location:
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  8. Article: Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy.

    Xu, Ning / Tse, Benjamin / Yang, Lu / Tang, Tiffany C Y / Haber, Michelle / Micklethwaite, Kenneth / Dolnikov, Alla

    ImmunoTargets and therapy

    2021  Volume 10, Page(s) 123–140

    Abstract: Purpose: Despite the success of chimeric antigen receptor (CAR) T cells in clinical studies, a significant proportion of responding patients eventually relapsed, with the latter correlating with low CAR T cell expansion and persistence.: Methods and ... ...

    Abstract Purpose: Despite the success of chimeric antigen receptor (CAR) T cells in clinical studies, a significant proportion of responding patients eventually relapsed, with the latter correlating with low CAR T cell expansion and persistence.
    Methods and results: Using patient-derived xenograft (PDX) mouse models of CD19
    Conclusion: We propose that treatment with AZA activates OX40L/OX40 co-stimulatory signaling in CAR T cells. Our data suggest that the clinical use of AZA before CAR T cells could be considered.
    Language English
    Publishing date 2021-04-28
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2706272-7
    ISSN 2253-1556
    ISSN 2253-1556
    DOI 10.2147/ITT.S296161
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  9. Article ; Online: CAR

    Louie, Raymond Hall Yip / Cai, Curtis / Samir, Jerome / Singh, Mandeep / Deveson, Ira W / Ferguson, James M / Amos, Timothy G / McGuire, Helen Marie / Gowrishankar, Kavitha / Adikari, Thiruni / Balderas, Robert / Bonomi, Martina / Ruella, Marco / Bishop, David / Gottlieb, David / Blyth, Emily / Micklethwaite, Kenneth / Luciani, Fabio

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 7767

    Abstract: Chimeric antigen receptor (CAR) T cell therapy is effective in treating B cell malignancies, but factors influencing the persistence of functional ... ...

    Abstract Chimeric antigen receptor (CAR) T cell therapy is effective in treating B cell malignancies, but factors influencing the persistence of functional CAR
    MeSH term(s) Humans ; Receptors, Antigen, T-Cell ; B-Lymphocytes ; Immunotherapy, Adoptive/methods ; Lymphoma, Large B-Cell, Diffuse/pathology ; T-Lymphocytes
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-11-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-43656-7
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  10. Article ; Online: Combining CD34+ stem cell selection with prophylactic pathogen and leukemia directed T-cell immunotherapy to simultaneously reduce graft versus host disease, infection, and leukemia recurrence after allogeneic stem cell transplant.

    Gottlieb, David J / Sutrave, Gaurav / Jiang, Wei / Avdic, Selmir / Street, Janine A / Simms, Renee / Clancy, Leighton E / Antonenas, Vicki / Gloss, Brian S / Bateman, Caroline / Bishop, David C / Micklethwaite, Kenneth P / Blyth, Emily

    American journal of hematology

    2022  Volume 98, Issue 1, Page(s) 159–165

    Abstract: We designed a trial to simultaneously address the problems of graft versus host disease (GVHD), infection, and recurrence of malignancy after allogeneic stem cell transplantation. ... ...

    Abstract We designed a trial to simultaneously address the problems of graft versus host disease (GVHD), infection, and recurrence of malignancy after allogeneic stem cell transplantation. CD34
    MeSH term(s) Humans ; T-Lymphocytes ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/therapy ; Transplantation, Homologous ; Treatment Outcome ; Herpesvirus 4, Human ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation ; Stem Cell Transplantation ; Immunotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
    Language English
    Publishing date 2022-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26594
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