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  1. Article ; Online: Immunocompromised host section: Adoptive T-cell therapy for dsDNA viruses in allogeneic hematopoietic cell transplant recipients.

    Walti, Carla S / Stuehler, Claudia / Palianina, Darya / Khanna, Nina

    Current opinion in infectious diseases

    2022  Volume 35, Issue 4, Page(s) 302–311

    Abstract: Purpose of review: Double-stranded DNA (dsDNA) viruses remain important causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As treatment options are limited, adoptive therapy with virus-specific T cells (VST) is ... ...

    Abstract Purpose of review: Double-stranded DNA (dsDNA) viruses remain important causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As treatment options are limited, adoptive therapy with virus-specific T cells (VST) is promising in restoring immunity and thereby preventing and treating virus infections. Here we review current evidence and recent advances in the field of VST for dsDNA viruses in allogeneic HCT recipients.
    Recent findings: Four different protocols for VST generation are currently used in clinical trials, and various products including multivirus-specific and off-the-shelf products are under investigation for prophylaxis, preemptive therapy or treatment. Data from nearly 1400 dsDNA-VST applications in allogeneic HCT patients have been published and demonstrated its safety. Although Epstein-Barr virus, cytomegalovirus, and adenovirus-specific T-cell therapy studies have predominated over the past 25 years, additional human herpes viruses were added to multivirus-specific T cells over the last decade and clinical evidence for polyomavirus-specific VST has just recently emerged. Response rates of around 70-80% have been reported, but cautious interpretation is warranted as data are predominantly from phase 1/2 studies and clinical efficacy needs to be confirmed in phase 3 studies.
    Summary: Investigation on the 'ideal' composition of VST is ongoing. Several products recently entered phase 3 trials and may allow widespread clinical use in the near future.
    MeSH term(s) Epstein-Barr Virus Infections/therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Herpesvirus 4, Human ; Humans ; Immunocompromised Host ; Transplant Recipients
    Language English
    Publishing date 2022-07-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 645085-4
    ISSN 1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
    ISSN (online) 1473-6527 ; 1535-3877
    ISSN 0951-7375 ; 1355-834X
    DOI 10.1097/QCO.0000000000000838
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A method for polyclonal antigen-specific T cell-targeted genome editing (TarGET) for adoptive cell transfer applications.

    Palianina, Darya / Di Roberto, Raphaël B / Castellanos-Rueda, Rocío / Schlatter, Fabrice / Reddy, Sai T / Khanna, Nina

    Molecular therapy. Methods & clinical development

    2023  Volume 30, Page(s) 147–160

    Abstract: Adoptive cell therapy of donor-derived, antigen-specific T cells expressing native T cell receptors (TCRs) is a powerful strategy to fight viral infections in immunocompromised patients. Determining the fate of T cells following patient infusion hinges ... ...

    Abstract Adoptive cell therapy of donor-derived, antigen-specific T cells expressing native T cell receptors (TCRs) is a powerful strategy to fight viral infections in immunocompromised patients. Determining the fate of T cells following patient infusion hinges on the ability to track them
    Language English
    Publishing date 2023-06-19
    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.2023.06.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: speedingCARs: accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing.

    Castellanos-Rueda, Rocío / Di Roberto, Raphaël B / Bieberich, Florian / Schlatter, Fabrice S / Palianina, Darya / Nguyen, Oanh T P / Kapetanovic, Edo / Läubli, Heinz / Hierlemann, Andreas / Khanna, Nina / Reddy, Sai T

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 6555

    Abstract: Chimeric antigen receptors (CARs) consist of an antigen-binding region fused to intracellular signaling domains, enabling customized T cell responses against targets. Despite their major role in T cell activation, effector function and persistence, only ... ...

    Abstract Chimeric antigen receptors (CARs) consist of an antigen-binding region fused to intracellular signaling domains, enabling customized T cell responses against targets. Despite their major role in T cell activation, effector function and persistence, only a small set of immune signaling domains have been explored. Here we present speedingCARs, an integrated method for engineering CAR T cells via signaling domain shuffling and pooled functional screening. Leveraging the inherent modularity of natural signaling domains, we generate a library of 180 unique CAR variants genomically integrated into primary human T cells by CRISPR-Cas9. In vitro tumor cell co-culture, followed by single-cell RNA sequencing (scRNA-seq) and single-cell CAR sequencing (scCAR-seq), enables high-throughput screening for identifying several variants with tumor killing properties and T cell phenotypes markedly different from standard CARs. Mapping of the CAR scRNA-seq data onto that of tumor infiltrating lymphocytes further helps guide the selection of variants. These results thus help expand the CAR signaling domain combination space, and supports speedingCARs as a tool for the engineering of CARs for potential therapeutic development.
    MeSH term(s) Humans ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes ; Signal Transduction ; Lymphocyte Activation ; Neoplasms ; Receptors, Antigen, T-Cell/genetics
    Chemical Substances Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2022-11-02
    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/s41467-022-34141-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: speedingCARs

    Castellanos-Rueda, Rocío / Di Roberto, Raphaël B. / Bieberich, Florian / Schlatter, Fabrice S. / id_orcid:0 000-0003-2192-6614 / Palianina, Darya / Nguyen, Thi Phuong Oanh / id_orcid:0 000-0003-0192-2456 / Kapetanovic, Edo / Läubli, Heinz / Hierlemann, Andreas / id_orcid:0 000-0002-3838-2468 / Khanna, Nina / Reddy, Sai T.

    Nature Communications, 13 (1)

    accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing

    2022  

    Abstract: Chimeric antigen receptors (CARs) consist of an antigen-binding region fused to intracellular signaling domains, enabling customized T cell responses against targets. Despite their major role in T cell activation, effector function and persistence, only ... ...

    Abstract Chimeric antigen receptors (CARs) consist of an antigen-binding region fused to intracellular signaling domains, enabling customized T cell responses against targets. Despite their major role in T cell activation, effector function and persistence, only a small set of immune signaling domains have been explored. Here we present speedingCARs, an integrated method for engineering CAR T cells via signaling domain shuffling and pooled functional screening. Leveraging the inherent modularity of natural signaling domains, we generate a library of 180 unique CAR variants genomically integrated into primary human T cells by CRISPR-Cas9. In vitro tumor cell co-culture, followed by single-cell RNA sequencing (scRNA-seq) and single-cell CAR sequencing (scCAR-seq), enables high-throughput screening for identifying several variants with tumor killing properties and T cell phenotypes markedly different from standard CARs. Mapping of the CAR scRNA-seq data onto that of tumor infiltrating lymphocytes further helps guide the selection of variants. These results thus help expand the CAR signaling domain combination space, and supports speedingCARs as a tool for the engineering of CARs for potential therapeutic development.

    ISSN:2041-1723
    Keywords Cancer immunotherapy ; Synthetic biology ; Transcriptomics ; Tumour immunology
    Subject code 572
    Language English
    Publishing date 2022-11-02
    Publisher Nature
    Publishing country ch
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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