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  1. Article: Intratumoral electroporation of a self-amplifying RNA expressing IL-12 induces antitumor effects in mouse models of cancer.

    Silva-Pilipich, Noelia / Lasarte-Cía, Aritz / Lozano, Teresa / Martín-Otal, Celia / Lasarte, Juan José / Smerdou, Cristian

    Molecular therapy. Nucleic acids

    2022  Volume 29, Page(s) 387–399

    Abstract: Alphavirus vectors based on self-amplifying RNA (saRNA) generate high and transient levels of transgene expression and induce innate immune responses, making them an interesting tool for antitumor therapy. These vectors are usually delivered as viral ... ...

    Abstract Alphavirus vectors based on self-amplifying RNA (saRNA) generate high and transient levels of transgene expression and induce innate immune responses, making them an interesting tool for antitumor therapy. These vectors are usually delivered as viral particles, but it is also possible to administer them as RNA. We evaluated this possibility by
    Language English
    Publishing date 2022-07-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2022.07.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Impact of tumor microenvironment on adoptive T cell transfer activity.

    Martín-Otal, Celia / Navarro, Flor / Casares, Noelia / Lasarte-Cía, Aritz / Sánchez-Moreno, Inés / Hervás-Stubbs, Sandra / Lozano, Teresa / Lasarte, Juan José

    International review of cell and molecular biology

    2022  Volume 370, Page(s) 1–31

    Abstract: Recent advances in immunotherapy have revolutionized the treatment of cancer. The use of adoptive cell therapies (ACT) such as those based on tumor infiltrating lymphocytes (TILs) or genetically modified cells (transgenic TCR lymphocytes or CAR-T cells), ...

    Abstract Recent advances in immunotherapy have revolutionized the treatment of cancer. The use of adoptive cell therapies (ACT) such as those based on tumor infiltrating lymphocytes (TILs) or genetically modified cells (transgenic TCR lymphocytes or CAR-T cells), has shown impressive results in the treatment of several types of cancers. However, cancer cells can exploit mechanisms to escape from immunosurveillance resulting in many patients not responding to these therapies or respond only transiently. The failure of immunotherapy to achieve long-term tumor control is multifactorial. On the one hand, only a limited percentage of the transferred lymphocytes is capable of circulating through the bloodstream, interacting and crossing the tumor endothelium to infiltrate the tumor. Metabolic competition, excessive glucose consumption, the high level of lactic acid secretion and the extracellular pH acidification, the shortage of essential amino acids, the hypoxic conditions or the accumulation of fatty acids in the tumor microenvironment (TME), greatly hinder the anti-tumor activity of the immune cells in ACT therapy strategies. Therefore, there is a new trend in immunotherapy research that seeks to unravel the fundamental biology that underpins the response to therapy and identifies new approaches to better amplify the efficacy of immunotherapies. In this review we address important aspects that may significantly affect the efficacy of ACT, indicating also the therapeutic alternatives that are currently being implemented to overcome these drawbacks.
    MeSH term(s) Humans ; Immunotherapy ; Immunotherapy, Adoptive/methods ; Lymphocytes, Tumor-Infiltrating ; Neoplasms/therapy ; T-Lymphocytes ; Tumor Microenvironment
    Language English
    Publishing date 2022-06-21
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2427220-6
    ISSN 1937-6448 ; 0074-7696
    ISSN 1937-6448 ; 0074-7696
    DOI 10.1016/bs.ircmb.2022.03.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.317: Show issues Location:
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  3. Article ; Online: Overcoming T cell dysfunction in acidic pH to enhance adoptive T cell transfer immunotherapy.

    Navarro, Flor / Casares, Noelia / Martín-Otal, Celia / Lasarte-Cía, Aritz / Gorraiz, Marta / Sarrión, Patricia / Llopiz, Diana / Reparaz, David / Varo, Nerea / Rodriguez-Madoz, Juan Roberto / Prosper, Felipe / Hervás-Stubbs, Sandra / Lozano, Teresa / Lasarte, Juan José

    Oncoimmunology

    2022  Volume 11, Issue 1, Page(s) 2070337

    Abstract: The high metabolic activity and insufficient perfusion of tumors leads to the acidification of the tumor microenvironment (TME) that may inhibit the antitumor T cell activity. We found that pharmacological inhibition of the acid loader chloride/ ... ...

    Abstract The high metabolic activity and insufficient perfusion of tumors leads to the acidification of the tumor microenvironment (TME) that may inhibit the antitumor T cell activity. We found that pharmacological inhibition of the acid loader chloride/bicarbonate anion exchanger 2 (Ae2), with 4,4'-diisothiocyanatostilbene-2,2'-disulfonicacid (DIDS) enhancedCD4
    MeSH term(s) 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/metabolism ; Animals ; CD8-Positive T-Lymphocytes/metabolism ; Cell Line, Tumor ; Hydrogen-Ion Concentration ; Immunotherapy, Adoptive/methods ; Mice
    Chemical Substances 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid (Q1O6DSW23R)
    Language English
    Publishing date 2022-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-4011
    ISSN (online) 2162-402X
    ISSN 2162-4011
    DOI 10.1080/2162402X.2022.2070337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Intratumoral STING Agonist Injection Combined with Irreversible Electroporation Delays Tumor Growth in a Model of Hepatocarcinoma.

    Lasarte-Cia, Aritz / Lozano, Teresa / Cano, David / Martín-Otal, Celia / Navarro, Flor / Gorraiz, Marta / Casares, Noelia / Vivas, Isabel / Lasarte, Juan José

    BioMed research international

    2021  Volume 2021, Page(s) 8852233

    Abstract: Background/aim: Irreversible electroporation (IRE) showed promising results for small-size tumors and very early cancers. However, further development is needed to evolve this procedure into a more efficient ablation technique for long-term control of ... ...

    Abstract Background/aim: Irreversible electroporation (IRE) showed promising results for small-size tumors and very early cancers. However, further development is needed to evolve this procedure into a more efficient ablation technique for long-term control of tumor growth. In this work, we show that it is possible to increase the antitumor efficiency of IRE by simmultaneously injecting c-di-GMP, a STING agonist, intratumorally.
    Materials and methods: Intratumoral administration of c-di-GMP simultaneously to IRE was evaluated in murine models of melanona (B16.OVA) and hepatocellular carcinoma (PM299L).
    Results: The combined therapy increased the number of tumor-infiltrating IFN-
    Conclusion: These results can lead to the development of a new therapeutic strategy for the treatment of cancer patients refractory to other therapies.
    MeSH term(s) Ablation Techniques/methods ; Animals ; Carcinoma, Hepatocellular/therapy ; Cell Line ; Combined Modality Therapy/methods ; Cyclic GMP/administration & dosage ; Cyclic GMP/analogs & derivatives ; Electroporation/methods ; Female ; Liver Neoplasms/therapy ; Liver Neoplasms, Experimental/therapy ; Membrane Proteins/agonists ; Mice, Inbred C57BL ; Mice
    Chemical Substances Membrane Proteins ; Sting1 protein, mouse ; bis(3',5')-cyclic diguanylic acid (61093-23-0) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2021-01-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2698540-8
    ISSN 2314-6141 ; 2314-6133
    ISSN (online) 2314-6141
    ISSN 2314-6133
    DOI 10.1155/2021/8852233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: TCR-induced FOXP3 expression by CD8

    Lozano, Teresa / Conde, Enrique / Martín-Otal, Celia / Navarro, Flor / Lasarte-Cia, Aritz / Nasrallah, Rabab / Alignani, Diego / Gorraiz, Marta / Sarobe, Pablo / Romero, Juan P / Vilas, Amaia / Roychoudhuri, Rahul / Hervás-Stubbs, Sandra / Casares, Noelia / Lasarte, Juan José

    Cancer letters

    2021  Volume 528, Page(s) 45–58

    Abstract: Adoptive cell transfer therapy using ... ...

    Abstract Adoptive cell transfer therapy using CD8
    Language English
    Publishing date 2021-12-29
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2021.12.030
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1177: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  6. Article ; Online: Targeting the extra domain A of fibronectin for cancer therapy with CAR-T cells.

    Martín-Otal, Celia / Lasarte-Cia, Aritz / Serrano, Diego / Casares, Noelia / Conde, Enrique / Navarro, Flor / Sánchez-Moreno, Inés / Gorraiz, Marta / Sarrión, Patricia / Calvo, Alfonso / De Andrea, Carlos E / Echeveste, José / Vilas, Amaia / Rodriguez-Madoz, Juan Roberto / San Miguel, Jesús / Prosper, Felipe / Hervas-Stubbs, Sandra / Lasarte, Juan Jose / Lozano, Teresa

    Journal for immunotherapy of cancer

    2022  Volume 10, Issue 8

    Abstract: Background: One of the main difficulties of adoptive cell therapies with chimeric antigen receptor (CAR)-T cells in solid tumors is the identification of specific target antigens. The tumor microenvironment can present suitable antigens for CAR design, ... ...

    Abstract Background: One of the main difficulties of adoptive cell therapies with chimeric antigen receptor (CAR)-T cells in solid tumors is the identification of specific target antigens. The tumor microenvironment can present suitable antigens for CAR design, even though they are not expressed by the tumor cells. We have generated a CAR specific for the splice variant extra domain A (EDA) of fibronectin, which is highly expressed in the tumor stroma of many types of tumors but not in healthy tissues.
    Methods: EDA expression was explored in RNA-seq data from different human tumor types and by immunohistochemistry in paraffin-embedded tumor biopsies. Murine and human anti-EDA CAR-T cells were prepared using recombinant retro/lentiviruses, respectively. The functionality of EDA CAR-T cells was measured in vitro in response to antigen stimulation. The antitumor activity of EDA CAR-T cells was measured in vivo in C57BL/6 mice challenged with PM299L-EDA hepatocarcinoma cell line, in 129Sv mice-bearing F9 teratocarcinoma and in NSG mice injected with the human hepatocarcinoma cell line PLC.
    Results: EDA CAR-T cells recognized and killed EDA-expressing tumor cell lines in vitro and rejected EDA-expressing tumors in immunocompetent mice. Notably, EDA CAR-T cells showed an antitumor effect in mice injected with EDA-negative tumor cells lines when the tumor stroma or the basement membrane of tumor endothelial cells express EDA. Thus, EDA CAR-T administration delayed tumor growth in immunocompetent 129Sv mice challenged with teratocarcinoma cell line F9. EDA CAR-T treatment exerted an antiangiogenic effect and significantly reduced gene signatures associated with epithelial-mesenchymal transition, collagen synthesis, extracellular matrix organization as well as IL-6-STAT5 and KRAS pathways. Importantly, the human version of EDA CAR, that includes the human 41BB and CD3ζ endodomains, exerted strong antitumor activity in NSG mice challenged with the human hepatocarcinoma cell line PLC, which expresses EDA in the tumor stroma and the endothelial vasculature. EDA CAR-T cells exhibited a tropism for EDA-expressing tumor tissue and no toxicity was observed in tumor bearing or in healthy mice.
    Conclusions: These results suggest that targeting the tumor-specific fibronectin splice variant EDA with CAR-T cells is feasible and offers a therapeutic option that is applicable to different types of cancer.
    MeSH term(s) Animals ; Endothelial Cells ; Fibronectins ; Humans ; Mice ; Mice, Inbred C57BL ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Teratocarcinoma/metabolism ; Tumor Microenvironment ; Xenograft Model Antitumor Assays
    Chemical Substances Fibronectins ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2022-07-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2021-004479
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  7. Article ; Online: CD300f immunoreceptor is associated with major depressive disorder and decreased microglial metabolic fitness.

    Lago, Natalia / Kaufmann, Fernanda N / Negro-Demontel, María Luciana / Alí-Ruiz, Daniela / Ghisleni, Gabriele / Rego, Natalia / Arcas-García, Andrea / Vitureira, Nathalia / Jansen, Karen / Souza, Luciano M / Silva, Ricardo A / Lara, Diogo R / Pannunzio, Bruno / Abin-Carriquiry, Juan Andrés / Amo-Aparicio, Jesús / Martin-Otal, Celia / Naya, Hugo / McGavern, Dorian B / Sayós, Joan /
    López-Vales, Rubèn / Kaster, Manuella P / Peluffo, Hugo

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 12, Page(s) 6651–6662

    Abstract: A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical ... ...

    Abstract A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f
    MeSH term(s) Anhedonia ; Animals ; Behavior, Animal ; Cohort Studies ; Depressive Disorder, Major/genetics ; Depressive Disorder, Major/metabolism ; Depressive Disorder, Major/pathology ; Depressive Disorder, Major/psychology ; Female ; Gene Expression Profiling ; Humans ; Inflammation/etiology ; Inflammation/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/metabolism ; Microglia/pathology ; Polymorphism, Single Nucleotide ; Receptors, Immunologic/genetics ; Receptors, Immunologic/physiology ; Synapses
    Chemical Substances CD300LF protein, human ; CLM-1 protein, mouse ; Receptors, Immunologic
    Language English
    Publishing date 2020-03-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1911816117
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
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