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  1. Article ; Online: Access offsets poverty in quest for CAR T cells.

    Rouce, Rayne H / Nemecek, Eneida

    Blood

    2023  Volume 141, Issue 6, Page(s) 558–560

    MeSH term(s) Humans ; Child ; Immunotherapy, Adoptive ; Poverty ; Antigens, CD19 ; T-Lymphocytes
    Chemical Substances Antigens, CD19
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2022018552
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.140: Show issues Location:
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  2. Article ; Online: Targeted cellular therapy for treatment of relapsed or refractory leukemia.

    Scherer, Lauren D / Rouce, Rayne H

    Best practice & research. Clinical haematology

    2023  Volume 36, Issue 3, Page(s) 101481

    Abstract: While the mainstay of treatment for high-risk or relapsed, refractory leukemia has historically revolved around allogeneic hematopoietic stem cell transplant (allo-HSCT), targeted immunotherapies have emerged as a promising therapeutic option, especially ...

    Abstract While the mainstay of treatment for high-risk or relapsed, refractory leukemia has historically revolved around allogeneic hematopoietic stem cell transplant (allo-HSCT), targeted immunotherapies have emerged as a promising therapeutic option, especially given the poor prognosis of patients who relapse after allo-HSCT. Novel cellular immunotherapies that harness the cytotoxic abilities of the immune system in a targeted manner (often called "adoptive" cell therapy), have changed the way we treat r/r hematologic malignancies and continue to change the treatment landscape given the rapid evolution of these powerful, yet sophisticated precision therapies that often offer a less toxic alternative to conventional salvage therapies. Importantly, adoptive cell therapy can be allo-HSCT-enabling or a therapeutic option for patients in whom transplantation has failed or is contraindicated. A solid understanding of the core concepts of adoptive cell therapy is necessary for stem cell transplant physicians, nurses and ancillary staff given its proximity to the transplant field as well as its inherent complexities that require specific expertise in compliant manufacturing, clinical application, and risk mitigation. Here we will review use of targeted cellular therapy for the treatment of r/r leukemia, focusing on chimeric antigen receptor T-cells (CAR T-cells) given the remarkable sustained clinical responses leading to commercial approval for several hematologic indications including leukemia, with brief discussion of other promising investigational cellular immunotherapies and special considerations for sustainability and scalability.
    MeSH term(s) Humans ; Immunotherapy ; Leukemia/therapy ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Cell- and Tissue-Based Therapy
    Language English
    Publishing date 2023-05-25
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2048027-1
    ISSN 1532-1924 ; 1521-6926
    ISSN (online) 1532-1924
    ISSN 1521-6926
    DOI 10.1016/j.beha.2023.101481
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  3. Article ; Online: Reverse translational studies inform dual-targeted CAR T-cell design.

    Rouce, Rayne H / Scherer, Lauren

    Blood

    2022  Volume 140, Issue 5, Page(s) 409–410

    MeSH term(s) Antigens, CD19 ; Child ; Humans ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes/immunology ; Young Adult
    Chemical Substances Antigens, CD19 ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2022-08-22
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2022016928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The earlier the better: timely mitigation of CRS.

    Rouce, Rayne H

    Blood

    2019  Volume 134, Issue 24, Page(s) 2119–2120

    MeSH term(s) Cytokine Release Syndrome ; Humans ; T-Lymphocytes
    Language English
    Publishing date 2019-12-11
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2019003618
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  5. Article ; Online: Chimeric antigen receptor T cells for mature B-cell lymphoma and Burkitt lymphoma.

    Hsieh, Emily M / Rouce, Rayne H

    Hematology. American Society of Hematology. Education Program

    2020  Volume 2020, Issue 1, Page(s) 487–493

    Abstract: Chimeric antigen receptor (CAR) T-cell therapy has changed the landscape of immunotherapy for B-cell malignancies, including mature B-cell lymphomas. Although two CD19 CAR T-cell products have been commercially approved to treat relapsed/refractory B- ... ...

    Abstract Chimeric antigen receptor (CAR) T-cell therapy has changed the landscape of immunotherapy for B-cell malignancies, including mature B-cell lymphomas. Although two CD19 CAR T-cell products have been commercially approved to treat relapsed/refractory B-cell lymphomas, outcomes in these patients remain inferior to those of patients with B-cell leukemia, regardless of therapy. Recent clinical studies and preclinical reports suggest that certain characteristics, such as the suppressive lymphoma tumor microenvironment and inferior endogenous T-cell fitness, may contribute to discrepant responses in these patients. In addition, these studies revealed that limited CAR T-cell persistence and tumor antigen escape, which also impact B-cell acute lymphoblastic leukemia, may play a more prominent role in lymphoma. Multiple promising strategies to overcome these barriers have advanced to clinical trials. In this review, we assess CAR T-cell therapies for pediatric relapsed/refractory mature B-cell lymphomas, potential obstacles diminishing antitumor activity and limiting CAR T-cell persistence, and current strategies to overcome these obstacles.
    MeSH term(s) Adolescent ; Burkitt Lymphoma/metabolism ; Burkitt Lymphoma/pathology ; Burkitt Lymphoma/therapy ; Humans ; Immunotherapy, Adoptive ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Receptors, Chimeric Antigen/therapeutic use ; Tumor Microenvironment
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2020-12-04
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2084287-9
    ISSN 1520-4383 ; 1520-4391
    ISSN (online) 1520-4383
    ISSN 1520-4391
    DOI 10.1182/hematology.2020000133
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: More than Memory: Potential of Adaptive Natural Killer Cells.

    Rouce, Rayne H

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2015  Volume 21, Issue 9, Page(s) 1534–1536

    MeSH term(s) Cord Blood Stem Cell Transplantation ; Cytomegalovirus/immunology ; Cytomegalovirus Infections/immunology ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Receptors, KIR/immunology ; Siblings
    Chemical Substances Receptors, KIR
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2015.07.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 462: Show issues

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  7. Article ; Online: Are we there yet? The never-ending quest for an Epstein-Barr virus vaccine.

    Sharma, Sandhya / Rouce, Rayne H

    The Journal of clinical investigation

    2019  Volume 129, Issue 5, Page(s) 1836–1838

    Abstract: The Epstein-Barr virus (EBV) is estimated to infect a large part of the population and is associated with a variety of human tumors; therefore, EBV is an important target for vaccine development. In this issue of the JCI, Rühl et al. developed a ... ...

    Abstract The Epstein-Barr virus (EBV) is estimated to infect a large part of the population and is associated with a variety of human tumors; therefore, EBV is an important target for vaccine development. In this issue of the JCI, Rühl et al. developed a promising heterologous prime-boost vaccination strategy for EBV-associated malignancies and symptomatic primary infection. The authors show that two prime-boost regimens, using either dendritic cells or an adenovirus approach targeting nuclear antigen EBNA1 followed by a modified vaccinia virus Ankara (MVA) booster, induced significant T cell-mediated, EBV-specific immune control and Ab production. These findings suggest that administration of heterologous prime-boost vaccinations targeting EBNA1 may result in potent CD4+ and CD8+ T cell-mediated EBV immune control and may be a promising clinical approach.
    MeSH term(s) CD8-Positive T-Lymphocytes ; Herpesvirus 4, Human ; Humans ; Lymphoma ; Vaccination ; Vaccinia virus
    Language English
    Publishing date 2019-04-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI128370
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  8. Article ; Online: Primed to Kill: CTV-1 Stimulated Haploidentical Natural Killer Cells for Consolidation of AML.

    Doherty, Erin / Rouce, Rayne H

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2018  Volume 24, Issue 8, Page(s) 1533–1535

    MeSH term(s) Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute ; Transplantation Conditioning
    Language English
    Publishing date 2018-06-20
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2018.06.019
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  9. Article ; Online: Replacing CAR-T cell resistance with persistence by changing a single residue.

    Hsieh, Emily M / Scherer, Lauren D / Rouce, Rayne H

    The Journal of clinical investigation

    2020  Volume 130, Issue 6, Page(s) 2806–2808

    Abstract: Sustained persistence of chimeric antigen receptor T (CAR-T) cells is a key characteristic associated with long-term remission in patients with hematologic malignancies. Attempts to uncover mechanisms that enhance persistence and thus functionality will ... ...

    Abstract Sustained persistence of chimeric antigen receptor T (CAR-T) cells is a key characteristic associated with long-term remission in patients with hematologic malignancies. Attempts to uncover mechanisms that enhance persistence and thus functionality will have a substantial impact in broadening application of CAR-T cell therapy, especially for solid tumors. In this issue of the JCI, Guedan et al. describe a promising strategy to limit T cell exhaustion and improve persistence by changing a single amino acid in the costimulatory domain of CD28. The authors demonstrated that this single amino acid substitution in CD28-based mesothelin CAR-T cells results in improved persistence and functionality in a xenograft model of pancreatic cancer. Furthermore, reciprocal alteration of the same residue in inducible costimulator-containing (ICOS-containing) CAR-T cells resulted in limited antitumor activity and persistence. These findings suggest that simple alterations in the costimulatory domain may enhance CAR-T cell persistence, warranting future evaluation in other CD28-costimulatory CARs in an effort to improve durable antitumor effects.
    MeSH term(s) Humans ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell/genetics ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes ; Xenograft Model Antitumor Assays
    Chemical Substances Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2020-05-04
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI136872
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  10. Article ; Online: Apoptosis of Hematopoietic Stem Cells Contributes to Bone Marrow Suppression Following Chimeric Antigen Receptor T Cell Therapy.

    Read, Jay A / Rouce, Rayne H / Mo, Feiyan / Mamonkin, Maksim / King, Katherine Y

    Transplantation and cellular therapy

    2022  Volume 29, Issue 3, Page(s) 165.e1–165.e7

    Abstract: Chimeric antigen receptor (CAR) T cell (CAR-T) therapy represents a revolutionary treatment for patients with relapsed/refractory hematologic malignancies. However, its use can result in significant toxicities, including cytokine release syndrome (CRS), ... ...

    Abstract Chimeric antigen receptor (CAR) T cell (CAR-T) therapy represents a revolutionary treatment for patients with relapsed/refractory hematologic malignancies. However, its use can result in significant toxicities, including cytokine release syndrome (CRS), a potentially life-threatening clinical syndrome resulting from the release of proinflammatory cytokines upon T cell activation. In addition, patients who develop CRS often experience prolonged cytopenias, and those with the most severe CRS also have the longest delays in full marrow recovery. Although an association between CRS and delayed bone marrow recovery has been established, the precise mechanism underlying this phenomenon remains unknown. This study was conducted to test our hypothesis that delayed bone marrow recovery following CAR-T therapy is caused by elevation of proinflammatory cytokines, leading to apoptosis and depletion of hematopoietic stem and progenitor cells (HSPCs). SCID-beige mice bearing intraperitoneal CD19
    MeSH term(s) Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow/pathology ; Bone Marrow Diseases/metabolism ; Bone Marrow Diseases/pathology ; Cytokines/metabolism ; Hematopoietic Stem Cells ; Interleukin-6/metabolism ; Mice, SCID ; Neoplasms ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive/adverse effects
    Chemical Substances Cytokines ; Interleukin-6 ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2022-12-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2022.12.020
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