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  1. Article ; Online: Multiomics-guided cellular immunotherapies.

    Legut, Mateusz

    Nature reviews. Cancer

    2023  Volume 23, Issue 6, Page(s) 348

    MeSH term(s) Humans ; Multiomics ; Immunotherapy/methods
    Language English
    Publishing date 2023-04-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/s41568-023-00570-w
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  2. Article: Endovascular treatment of infrarenal aortic aneurysm using the ANKURA stent graft - one-center case series.

    Nowakowski, Przemysław / Uchto, Wojciech / Stoliński, Jarosław / Gubała, Marek / Legut, Mateusz

    Postepy w kardiologii interwencyjnej = Advances in interventional cardiology

    2023  Volume 19, Issue 1, Page(s) 67–69

    Language English
    Publishing date 2023-01-11
    Publishing country Poland
    Document type Journal Article
    ISSN 1734-9338
    ISSN 1734-9338
    DOI 10.5114/aic.2023.124041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ligand Identification for Orphan MHC-Agnostic T-Cell Receptors by Whole Genome CRISPR-Cas9 Screening.

    Crowther, Michael D / Legut, Mateusz / Sewell, Andrew K

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2574, Page(s) 3–14

    Abstract: Killer T-cells play important roles in immunity to infection and cancer by detecting intracellular anomalies at the cell surface and destroying the cells that bear them. Conventional killer T-cells scan the intracellular proteome by sampling peptides ... ...

    Abstract Killer T-cells play important roles in immunity to infection and cancer by detecting intracellular anomalies at the cell surface and destroying the cells that bear them. Conventional killer T-cells scan the intracellular proteome by sampling peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. It is becoming apparent that some T-cells can also respond to pathogens and neoplasms by sensing intracellular changes through molecules other than MHC. We describe an unbiased methodology for T-cell receptor ligand discovery that requires no a priori knowledge regarding the nature of the antigen.
    MeSH term(s) CRISPR-Cas Systems ; Histocompatibility Antigens ; Ligands ; Major Histocompatibility Complex ; Receptors, Antigen, T-Cell/genetics
    Chemical Substances Histocompatibility Antigens ; Ligands ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2022-09-10
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2712-9_1
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  4. Article ; Online: Immunomagnetic cell sorting.

    Legut, Mateusz / Sanjana, Neville E

    Nature biomedical engineering

    2019  Volume 3, Issue 10, Page(s) 759–760

    MeSH term(s) Clustered Regularly Interspaced Short Palindromic Repeats ; Cost-Benefit Analysis ; Flow Cytometry/methods ; Genes, Neoplasm ; Genome, Human ; Humans ; Immunomagnetic Separation/methods ; Immunotherapy/methods ; Lab-On-A-Chip Devices
    Language English
    Publishing date 2019-09-23
    Publishing country England
    Document type Journal Article
    ISSN 2157-846X
    ISSN (online) 2157-846X
    DOI 10.1038/s41551-019-0459-3
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  5. Article ; Online: Publisher Correction: Recurrent somatic mutations as predictors of immunotherapy response.

    Gajic, Zoran Z / Deshpande, Aditya / Legut, Mateusz / Imieliński, Marcin / Sanjana, Neville E

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 4558

    Language English
    Publishing date 2022-08-05
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-32460-4
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  6. Article ; Online: Designer T-cells and T-cell receptors for customized cancer immunotherapies.

    Legut, Mateusz / Sewell, Andrew K

    Current opinion in pharmacology

    2018  Volume 41, Page(s) 96–103

    Abstract: Cancer immunotherapy, focused on harnessing and empowering the immune system against tumours, has transformed modern oncology. One of the most promising avenues in development involves using genetically engineered T-cells to target cancer antigens via ... ...

    Abstract Cancer immunotherapy, focused on harnessing and empowering the immune system against tumours, has transformed modern oncology. One of the most promising avenues in development involves using genetically engineered T-cells to target cancer antigens via specific T-cell receptors (TCRs). TCRs have a naturally low affinity towards cancer-associated antigens, and therefore show scope for improvement. Here we describe approaches to procure TCRs with enhanced affinity and specificity towards cancer, using protein engineering or selection of natural TCRs from unadulterated repertoires. In particular, we discuss novel methods facilitating the targeting of tumour-specific mutations. Finally, we provide a prospective outlook on the potential development of novel, off-the-shelf immunotherapies by leveraging recent advances in genome editing.
    MeSH term(s) Antigens, Neoplasm/immunology ; Humans ; Immunotherapy/methods ; Neoplasms/immunology ; Neoplasms/therapy ; Protein Engineering ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/immunology
    Chemical Substances Antigens, Neoplasm ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2018-05-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2037057-X
    ISSN 1471-4973 ; 1471-4892
    ISSN (online) 1471-4973
    ISSN 1471-4892
    DOI 10.1016/j.coph.2018.05.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Recurrent somatic mutations as predictors of immunotherapy response.

    Gajic, Zoran Z / Deshpande, Aditya / Legut, Mateusz / Imieliński, Marcin / Sanjana, Neville E

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 3938

    Abstract: Immune checkpoint blockade (ICB) has transformed the treatment of metastatic cancer but is hindered by variable response rates. A key unmet need is the identification of biomarkers that predict treatment response. To address this, we analyzed six whole ... ...

    Abstract Immune checkpoint blockade (ICB) has transformed the treatment of metastatic cancer but is hindered by variable response rates. A key unmet need is the identification of biomarkers that predict treatment response. To address this, we analyzed six whole exome sequencing cohorts with matched disease outcomes to identify genes and pathways predictive of ICB response. To increase detection power, we focus on genes and pathways that are significantly mutated following correction for epigenetic, replication timing, and sequence-based covariates. Using this technique, we identify several genes (BCLAF1, KRAS, BRAF, and TP53) and pathways (MAPK signaling, p53 associated, and immunomodulatory) as predictors of ICB response and develop the Cancer Immunotherapy Response CLassifiEr (CIRCLE). Compared to tumor mutational burden alone, CIRCLE led to superior prediction of ICB response with a 10.5% increase in sensitivity and a 11% increase in specificity. We envision that CIRCLE and more broadly the analysis of recurrently mutated cancer genes will pave the way for better prognostic tools for cancer immunotherapy.
    MeSH term(s) Biomarkers, Tumor/metabolism ; Humans ; Immunotherapy/methods ; Mutation ; Neoplasms/genetics ; Neoplasms/therapy ; Whole Exome Sequencing
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2022-07-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-31055-3
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  8. Article ; Online: Publisher Correction

    Zoran Z. Gajic / Aditya Deshpande / Mateusz Legut / Marcin Imieliński / Neville E. Sanjana

    Nature Communications, Vol 13, Iss 1, Pp 1-

    Recurrent somatic mutations as predictors of immunotherapy response

    2022  Volume 1

    Keywords Science ; Q
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Massively parallel Cas13 screens reveal principles for guide RNA design.

    Wessels, Hans-Hermann / Méndez-Mancilla, Alejandro / Guo, Xinyi / Legut, Mateusz / Daniloski, Zharko / Sanjana, Neville E

    Nature biotechnology

    2020  Volume 38, Issue 6, Page(s) 722–727

    Abstract: Type VI CRISPR enzymes are RNA-targeting proteins with nuclease activity that enable specific and robust target gene knockdown without altering the genome. To define rules for the design of Cas13d guide RNAs (gRNAs), we conducted massively parallel ... ...

    Abstract Type VI CRISPR enzymes are RNA-targeting proteins with nuclease activity that enable specific and robust target gene knockdown without altering the genome. To define rules for the design of Cas13d guide RNAs (gRNAs), we conducted massively parallel screens targeting messenger RNAs (mRNAs) of a green fluorescent protein transgene, and CD46, CD55 and CD71 cell-surface proteins in human cells. In total, we measured the activity of 24,460 gRNAs with and without mismatches relative to the target sequences. Knockdown efficacy is driven by gRNA-specific features and target site context. Single mismatches generally reduce knockdown to a modest degree, but spacer nucleotides 15-21 are largely intolerant of target site mismatches. We developed a computational model to identify optimal gRNAs and confirm their generalizability, testing 3,979 guides targeting mRNAs of 48 endogenous genes. We show that Cas13 can be used in forward transcriptomic pooled screens and, using our model, predict optimized Cas13 gRNAs for all protein-coding transcripts in the human genome.
    MeSH term(s) CRISPR-Cas Systems/genetics ; Computational Biology/methods ; Gene Editing/methods ; Gene Knockdown Techniques/methods ; HEK293 Cells ; Humans ; Sequence Analysis, RNA ; RNA, Guide, CRISPR-Cas Systems
    Chemical Substances RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2020-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-020-0456-9
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  10. Article ; Online: A genome-scale screen for synthetic drivers of T cell proliferation.

    Legut, Mateusz / Gajic, Zoran / Guarino, Maria / Daniloski, Zharko / Rahman, Jahan A / Xue, Xinhe / Lu, Congyi / Lu, Lu / Mimitou, Eleni P / Hao, Stephanie / Davoli, Teresa / Diefenbach, Catherine / Smibert, Peter / Sanjana, Neville E

    Nature

    2022  Volume 603, Issue 7902, Page(s) 728–735

    Abstract: The engineering of autologous patient T cells for adoptive cell therapies has revolutionized the treatment of several types of ... ...

    Abstract The engineering of autologous patient T cells for adoptive cell therapies has revolutionized the treatment of several types of cancer
    MeSH term(s) CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cell Proliferation ; Humans ; Immunotherapy, Adoptive ; Lymphocyte Activation/genetics ; Neoplasms
    Language English
    Publishing date 2022-03-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-04494-7
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