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  1. Article: Dr. T. R. Gururaja Rao.

    Smitha, T

    Journal of oral and maxillofacial pathology : JOMFP

    2019  Volume 23, Issue 2, Page(s) 170–171

    Language English
    Publishing date 2019-06-10
    Publishing country India
    Document type Journal Article
    ZDB-ID 2390999-7
    ISSN 1998-393X ; 0973-029X
    ISSN (online) 1998-393X
    ISSN 0973-029X
    DOI 10.4103/jomfp.JOMFP_169_19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Lymphomatous Meningitis From Anaplastic Lymphoma Kinase+ Anaplastic Large T-Cell Lymphoma Treated With Lorlatinib: A Case Report.

    Mellacheruvu, Smitha / Sayegh, Mark N / Sica, R Alejandro / Cheng, Haiying / Santos-Zabala, Maria Laureana / Gebrael, Jacob H / Hermanto, Ulrich / Rosen, Norman L

    JCO precision oncology

    2022  Volume 6, Page(s) e2100250

    MeSH term(s) Aminopyridines ; Anaplastic Lymphoma Kinase ; Humans ; Lactams ; Lymphoma, T-Cell/drug therapy ; Meningitis ; Pyrazoles/therapeutic use
    Chemical Substances Aminopyridines ; Lactams ; Pyrazoles ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; lorlatinib (OSP71S83EU)
    Language English
    Publishing date 2022-02-09
    Publishing country United States
    Document type Case Reports ; Journal Article
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.21.00250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers.

    Smith, Tyrel T / Stephan, Sirkka B / Moffett, Howell F / McKnight, Laura E / Ji, Weihang / Reiman, Diana / Bonagofski, Emmy / Wohlfahrt, Martin E / Pillai, Smitha P S / Stephan, Matthias T

    Nature nanotechnology

    2017  Volume 12, Issue 8, Page(s) 813–820

    Abstract: An emerging approach for treating cancer involves programming patient-derived T cells with genes ... they require to generate large numbers of tumour-specific T cells are too elaborate for widespread application ... to treat cancer patients. Here, we describe a method to quickly program circulating T cells with tumour ...

    Abstract An emerging approach for treating cancer involves programming patient-derived T cells with genes encoding disease-specific chimeric antigen receptors (CARs), so that they can combat tumour cells once they are reinfused. Although trials of this therapy have produced impressive results, the in vitro methods they require to generate large numbers of tumour-specific T cells are too elaborate for widespread application to treat cancer patients. Here, we describe a method to quickly program circulating T cells with tumour-recognizing capabilities, thus avoiding these complications. Specifically, we demonstrate that DNA-carrying nanoparticles can efficiently introduce leukaemia-targeting CAR genes into T-cell nuclei, thereby bringing about long-term disease remission. These polymer nanoparticles are easy to manufacture in a stable form, which simplifies storage and reduces cost. Our technology may therefore provide a practical, broadly applicable treatment that can generate anti-tumour immunity 'on demand' for oncologists in a variety of settings.
    MeSH term(s) Animals ; Cell Line, Tumor ; DNA/chemistry ; Drug Carriers/chemistry ; Drug Carriers/pharmacology ; Gene Transfer Techniques ; Immunity, Cellular/drug effects ; Immunity, Cellular/genetics ; Leukemia/genetics ; Leukemia/immunology ; Leukemia/pathology ; Leukemia/therapy ; Mice ; Nanoparticles/chemistry ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology
    Chemical Substances Drug Carriers ; Receptors, Chimeric Antigen ; DNA (9007-49-2)
    Language English
    Publishing date 2017-04-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2254964-X
    ISSN 1748-3395 ; 1748-3387
    ISSN (online) 1748-3395
    ISSN 1748-3387
    DOI 10.1038/nnano.2017.57
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Off-the-shelf Vδ1 gamma delta T cells engineered with glypican-3 (GPC-3)-specific chimeric antigen receptor (CAR) and soluble IL-15 display robust antitumor efficacy against hepatocellular carcinoma.

    Makkouk, Amani / Yang, Xue Cher / Barca, Taylor / Lucas, Anthony / Turkoz, Mustafa / Wong, Jonathan T S / Nishimoto, Kevin P / Brodey, Mary M / Tabrizizad, Maryam / Gundurao, Smitha R Y / Bai, Lu / Bhat, Arun / An, Zili / Abbot, Stewart / Satpayev, Daulet / Aftab, Blake T / Herrman, Marissa

    Journal for immunotherapy of cancer

    2021  Volume 9, Issue 12

    Abstract: ... relevance in hepatocellular carcinoma (HCC). Autologous chimeric antigen receptor (CAR) αβ T cell therapies ... tumors has been limited due to several challenges including T cell homing, target antigen heterogeneity ... and immunosuppressive tumor microenvironments. Gamma delta (γδ) T cells are highly cytolytic effectors ...

    Abstract Background: Glypican-3 (GPC-3) is an oncofetal protein that is highly expressed in various solid tumors, but rarely expressed in healthy adult tissues and represents a rational target of particular relevance in hepatocellular carcinoma (HCC). Autologous chimeric antigen receptor (CAR) αβ T cell therapies have established significant clinical benefit in hematologic malignancies, although efficacy in solid tumors has been limited due to several challenges including T cell homing, target antigen heterogeneity, and immunosuppressive tumor microenvironments. Gamma delta (γδ) T cells are highly cytolytic effectors that can recognize and kill tumor cells through major histocompatibility complex (MHC)-independent antigens upregulated under stress. The Vδ1 subset is preferentially localized in peripheral tissue and engineering with CARs to further enhance intrinsic antitumor activity represents an attractive approach to overcome challenges for conventional T cell therapies in solid tumors. Allogeneic Vδ1 CAR T cell therapy may also overcome other hurdles faced by allogeneic αβ T cell therapy, including graft-versus-host disease (GvHD).
    Methods: We developed the first example of allogeneic CAR Vδ1 T cells that have been expanded from peripheral blood mononuclear cells (PBMCs) and genetically modified to express a 4-1BB/CD3z CAR against GPC-3. The CAR construct (GPC-3.CAR/secreted interleukin-15 (sIL)-15) additionally encodes a constitutively-secreted form of IL-15, which we hypothesized could sustain proliferation and antitumor activity of intratumoral Vδ1 T cells expressing GPC-3.CAR.
    Results: GPC-3.CAR/sIL-15 Vδ1 T cells expanded from PBMCs on average 20,000-fold and routinely reached >80% purity. Expanded Vδ1 T cells showed a primarily naïve-like memory phenotype with limited exhaustion marker expression and displayed robust in vitro proliferation, cytokine production, and cytotoxic activity against HCC cell lines expressing low (PLC/PRF/5) and high (HepG2) GPC-3 levels. In a subcutaneous HepG2 mouse model in immunodeficient NSG mice, GPC-3.CAR/sIL-15 Vδ1 T cells primarily accumulated and proliferated in the tumor, and a single dose efficiently controlled tumor growth without evidence of xenogeneic GvHD. Importantly, compared with GPC-3.CAR Vδ1 T cells lacking sIL-15, GPC-3.CAR/sIL-15 Vδ1 T cells displayed greater proliferation and resulted in enhanced therapeutic activity.
    Conclusions: Expanded Vδ1 T cells engineered with a GPC-3 CAR and sIL-15 represent a promising platform warranting further clinical evaluation as an off-the-shelf treatment of HCC and potentially other GPC-3-expressing solid tumors.
    MeSH term(s) Animals ; Apoptosis ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/immunology ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/therapy ; Cell Proliferation ; Female ; Glypicans/immunology ; Humans ; Immunotherapy, Adoptive/methods ; Interleukin-15/immunology ; Leukocytes, Mononuclear ; Liver Neoplasms/genetics ; Liver Neoplasms/immunology ; Liver Neoplasms/pathology ; Liver Neoplasms/therapy ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Receptors, Chimeric Antigen/immunology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
    Chemical Substances GPC3 protein, human ; Glypicans ; IL15 protein, human ; Interleukin-15 ; Receptors, Antigen, T-Cell, gamma-delta ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2021-12-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2021-003441
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Dysregulation of type 2 innate lymphoid cells and T

    De Grove, Katrien C / Provoost, Sharen / Hendriks, Rudi W / McKenzie, Andrew N J / Seys, Leen J M / Kumar, Smitha / Maes, Tania / Brusselle, Guy G / Joos, Guy F

    The Journal of allergy and clinical immunology

    2016  Volume 139, Issue 1, Page(s) 246–257.e4

    Abstract: Background: Although the prominent role of T: Objective: We sought to investigate the relative ... contribution of ILC2 and adaptive T: Methods: Wild-type, Gata-3: Results: Concomitant DEP+HDM exposure ... goblet cell metaplasia, accumulation of ILC2s and T: Conclusion: These data indicate that dysregulation ...

    Abstract Background: Although the prominent role of T
    Objective: We sought to investigate the relative contribution of ILC2 and adaptive T
    Methods: Wild-type, Gata-3
    Results: Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and T
    Conclusion: These data indicate that dysregulation of ILC2s and T
    MeSH term(s) Adaptive Immunity ; Air Pollutants ; Animals ; Antigens, Dermatophagoides/immunology ; Bronchoalveolar Lavage Fluid/immunology ; Cells, Cultured ; Cytokines/immunology ; Female ; GATA3 Transcription Factor/immunology ; Immunity, Innate ; Lung/immunology ; Lung/pathology ; Lymph Nodes/immunology ; Lymphocytes/immunology ; Mice, Inbred C57BL ; Mice, Transgenic ; Particulate Matter ; Respiratory Hypersensitivity/chemically induced ; Respiratory Hypersensitivity/immunology ; Respiratory Hypersensitivity/pathology ; Respiratory Hypersensitivity/physiopathology ; Vehicle Emissions
    Chemical Substances Air Pollutants ; Antigens, Dermatophagoides ; Cytokines ; GATA3 Transcription Factor ; Gata3 protein, mouse ; Particulate Matter ; Vehicle Emissions
    Language English
    Publishing date 2016-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2016.03.044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.92: Show issues Location:
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  6. Article: From editor's desk.

    Smitha, T

    Journal of oral and maxillofacial pathology : JOMFP

    2023  Volume 27, Issue 2, Page(s) 245

    Language English
    Publishing date 2023-07-13
    Publishing country India
    Document type Editorial
    ZDB-ID 2390999-7
    ISSN 1998-393X ; 0973-029X
    ISSN (online) 1998-393X
    ISSN 0973-029X
    DOI 10.4103/jomfp.jomfp_239_23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: From editor's desk.

    Smitha, T

    Journal of oral and maxillofacial pathology : JOMFP

    2023  Volume 27, Issue 3, Page(s) 431

    Language English
    Publishing date 2023-09-12
    Publishing country India
    Document type Editorial
    ZDB-ID 2390999-7
    ISSN 1998-393X ; 0973-029X
    ISSN (online) 1998-393X
    ISSN 0973-029X
    DOI 10.4103/jomfp.jomfp_369_23
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  8. Article: From the editor's desk.

    Smitha, T

    Journal of oral and maxillofacial pathology : JOMFP

    2023  Volume 27, Issue 1, Page(s) 1

    Language English
    Publishing date 2023-03-21
    Publishing country India
    Document type Editorial
    ZDB-ID 2390999-7
    ISSN 1998-393X ; 0973-029X
    ISSN (online) 1998-393X
    ISSN 0973-029X
    DOI 10.4103/jomfp.jomfp_101_23
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  9. Article: Editorial.

    Smitha, T

    Journal of oral and maxillofacial pathology : JOMFP

    2023  Volume 27, Issue 4, Page(s) 609

    Language English
    Publishing date 2023-12-20
    Publishing country India
    Document type Editorial
    ZDB-ID 2390999-7
    ISSN 1998-393X ; 0973-029X
    ISSN (online) 1998-393X
    ISSN 0973-029X
    DOI 10.4103/jomfp.jomfp_482_23
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  10. Article ; Online: Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors.

    Smith, Tyrel T / Moffett, Howell F / Stephan, Sirkka B / Opel, Cary F / Dumigan, Amy G / Jiang, Xiuyun / Pillarisetty, Venu G / Pillai, Smitha P S / Wittrup, K Dane / Stephan, Matthias T

    The Journal of clinical investigation

    2017  Volume 127, Issue 6, Page(s) 2176–2191

    Abstract: Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T ... cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments ... CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell ...

    Abstract Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.
    MeSH term(s) Adoptive Transfer ; Animals ; Antigen-Presenting Cells/physiology ; Antineoplastic Agents/administration & dosage ; Biopolymers/administration & dosage ; Carcinoma, Pancreatic Ductal/immunology ; Carcinoma, Pancreatic Ductal/therapy ; Cell Line, Tumor ; Cyclic GMP/administration & dosage ; Cyclic GMP/analogs & derivatives ; Drug Carriers/administration & dosage ; Female ; Implants, Experimental ; Melanoma, Experimental/immunology ; Melanoma, Experimental/therapy ; Membrane Proteins/agonists ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasm Transplantation ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/therapy ; T-Lymphocytes/physiology
    Chemical Substances Antineoplastic Agents ; Biopolymers ; Drug Carriers ; Membrane Proteins ; Sting1 protein, mouse ; bis(3',5')-cyclic diguanylic acid (61093-23-0) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2017-04-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI87624
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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
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