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  1. Book ; Thesis: Expression and function of c-Myc and N-Myc in adult hematopoietic stem cells during homeostasis and stress

    Ehninger, Armin

    2011  

    Author's details [presented by Armin Ehninger]
    Subject code 573.155383519353
    Language English
    Size XVI, 177 S. : Ill., graph. Darst., 30 cm
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Heidelberg, Univ., Diss., 2011
    HBZ-ID HT016966293
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: Chimeric antigen receptor T-cell therapy in acute myeloid leukemia.

    Koedam, Jan / Wermke, Martin / Ehninger, Armin / Cartellieri, Marc / Ehninger, Gerhard

    Current opinion in hematology

    2022  Volume 29, Issue 2, Page(s) 74–83

    Abstract: Purpose of review: Treatment outcome of relapsed or refractory AML patients remains dismal and new treatment options are needed. Adoptive cell therapy using CAR-T cells is a potentially interesting approach in this.: Recent findings: Several ... ...

    Abstract Purpose of review: Treatment outcome of relapsed or refractory AML patients remains dismal and new treatment options are needed. Adoptive cell therapy using CAR-T cells is a potentially interesting approach in this.
    Recent findings: Several potentially interesting AML targets are being investigated with CAR-T therapy with over 60 clinical trials listed on clinicaltrials.gov. The first clinical data are only just emerging with mixed results, once more proving that further research is needed.
    Summary: Adoptive cell therapy using chimeric antigen receptor T cells is being investigated in AML through many clinical trials. So far, no AML-specific antigen has been identified, requiring additional strategies to mitigate on-target off-tumor toxicity and to increase efficacy. Focus point is to acquire control over the CAR T cells once administered. Strategies to do so include biodegradable CARs, inducible CARs, suicide-switch containing CARs and two-component modular CARs. Limited and mixed results are available, confirming the risk of lasting toxicity for nonswitchable CARs. Initial results of modular CARs suggest toxicity can be mitigated whilst maintaining CAR activity by the use of modular CAR concepts that allows for 'ON' and 'OFF' switching.
    MeSH term(s) Cell- and Tissue-Based Therapy ; Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Leukemia, Myeloid, Acute/pathology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/therapeutic use ; Receptors, Chimeric Antigen
    Chemical Substances Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1153887-9
    ISSN 1531-7048 ; 1065-6251
    ISSN (online) 1531-7048
    ISSN 1065-6251
    DOI 10.1097/MOH.0000000000000703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Thesis: Expression and function of C-Myc and N-Myc in adult hematopoietic stem cells during homeostasis and stress

    Ehninger, Armin

    2011  

    Author's details [presented by Armin Ehninger]
    Language English
    Size XVI, 177 S., Ill., graph. Darst.
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Heidelberg, 2011
    Note Zsfassung in dt. und engl. Sprache
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  4. Article ; Online: Proof of concept for a rapidly switchable universal CAR-T platform with UniCAR-T-CD123 in relapsed/refractory AML.

    Wermke, Martin / Kraus, Sabrina / Ehninger, Armin / Bargou, Ralf C / Goebeler, Maria-Elisabeth / Middeke, Jan Moritz / Kreissig, Carla / von Bonin, Malte / Koedam, Jan / Pehl, Michael / Bornhäuser, Martin / Einsele, Hermann / Ehninger, Gerhard / Cartellieri, Marc

    Blood

    2021  Volume 137, Issue 22, Page(s) 3145–3148

    MeSH term(s) Aged ; Aged, 80 and over ; Humans ; Immunotherapy, Adoptive ; Leukemia, Myeloid, Acute/therapy ; Male ; Middle Aged ; Proof of Concept Study ; Receptors, Chimeric Antigen/administration & dosage
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2021-02-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2020009759
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML.

    Meyer, Jan-Erik / Loff, Simon / Dietrich, Josephine / Spehr, Johannes / Jurado Jiménez, Gabriel / von Bonin, Malte / Ehninger, Gerhard / Cartellieri, Marc / Ehninger, Armin

    Oncoimmunology

    2021  Volume 10, Issue 1, Page(s) 1945804

    Abstract: Chimeric antigen receptor T cells (CAR-T) targeting CD19 have achieved significant success in patients with B cell malignancies. To date, implementation of CAR-T in other indications remains challenging due to the lack of truly tumor-specific antigens as ...

    Abstract Chimeric antigen receptor T cells (CAR-T) targeting CD19 have achieved significant success in patients with B cell malignancies. To date, implementation of CAR-T in other indications remains challenging due to the lack of truly tumor-specific antigens as well as control of CAR-T activity in patients. CD123 is highly expressed in acute myeloid leukemia (AML) blasts including leukemia-initiating cells making it an attractive immunotherapeutic target. However, CD123 expression in normal hematopoietic progenitor cells and endothelia bears the risk of severe toxicities and may limit CAR-T applications lacking fine-tuned control mechanisms. Therefore, we recently developed a rapidly switchable universal CAR-T platform (UniCAR), in which CAR-T activity depends on the presence of a soluble adapter called targeting module (TM), and confirmed clinical proof-of-concept for targeting CD123 in AML with improved safety. As costimulation via 4-1BB ligand (4-1BBL) can enhance CAR-T expansion, persistence, and effector functions, a novel CD123-specific TM variant (TM123-4-1BBL) comprising trimeric single-chain 4-1BBL was developed for transient costimulation of UniCAR-T cells (UniCAR-T) at the leukemic site
    MeSH term(s) Antigens, Neoplasm ; Humans ; Immunotherapy, Adoptive ; Interleukin-3 Receptor alpha Subunit ; Leukemia, Myeloid, Acute/drug therapy ; T-Lymphocytes
    Chemical Substances Antigens, Neoplasm ; Interleukin-3 Receptor alpha Subunit
    Language English
    Publishing date 2021-07-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-4011
    ISSN (online) 2162-402X
    ISSN 2162-4011
    DOI 10.1080/2162402X.2021.1945804
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Rapidly Switchable Universal CAR-T Cells for Treatment of CD123-Positive Leukemia.

    Loff, Simon / Dietrich, Josephine / Meyer, Jan-Erik / Riewaldt, Julia / Spehr, Johannes / von Bonin, Malte / Gründer, Cordula / Swayampakula, Mridula / Franke, Kristin / Feldmann, Anja / Bachmann, Michael / Ehninger, Gerhard / Ehninger, Armin / Cartellieri, Marc

    Molecular therapy oncolytics

    2020  Volume 17, Page(s) 408–420

    Abstract: Chimeric antigen receptor T cells (CAR-T) targeting CD19 or B cell maturation antigen (BCMA) are highly effective against B cell malignancies. However, application of CAR-T to less differentially expressed targets remains a challenge due to lack of tumor- ...

    Abstract Chimeric antigen receptor T cells (CAR-T) targeting CD19 or B cell maturation antigen (BCMA) are highly effective against B cell malignancies. However, application of CAR-T to less differentially expressed targets remains a challenge due to lack of tumor-specific antigens and CAR-T controllability. CD123, a highly promising leukemia target, is expressed not only by leukemic and leukemia-initiating cells, but also by myeloid, hematopoietic progenitor, and certain endothelial cells. Thus, CAR-T lacking fine-tuned control mechanisms pose a high toxicity risk. To extend the CAR-T target landscape and widen the therapeutic window, we adapted our rapidly switchable universal CAR-T platform (UniCAR) to target CD123. UniCAR-T efficiently eradicated CD123
    Language English
    Publishing date 2020-04-29
    Publishing country United States
    Document type Journal Article
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2020.04.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in.

    Ehninger, Armin / Trumpp, Andreas

    The Journal of experimental medicine

    2011  Volume 208, Issue 3, Page(s) 421–428

    Abstract: Stem cell niches are defined as the cellular and molecular microenvironments that regulate stem cell function together with stem cell autonomous mechanisms. This includes control of the balance between quiescence, self-renewal, and differentiation, as ... ...

    Abstract Stem cell niches are defined as the cellular and molecular microenvironments that regulate stem cell function together with stem cell autonomous mechanisms. This includes control of the balance between quiescence, self-renewal, and differentiation, as well as the engagement of specific programs in response to stress. In mammals, the best understood niche is that harboring bone marrow hematopoietic stem cells (HSCs). Recent studies have expanded the number of cell types contributing to the HSC niche. Perivascular mesenchymal stem cells and macrophages now join the previously identified sinusoidal endothelial cells, sympathetic nerve fibers, and cells of the osteoblastic lineage to form similar, but distinct, niches that harbor dormant and self-renewing HSCs during homeostasis and mediate stem cell mobilization in response to granulocyte colony-stimulating factor.
    MeSH term(s) Animals ; Bone Marrow/growth & development ; Bone Marrow/physiology ; Granulocyte Colony-Stimulating Factor/physiology ; Humans ; Macrophages/physiology ; Mesenchymal Stem Cells/physiology ; Monocytes/physiology ; Stem Cell Niche/cytology ; Stem Cell Niche/physiology
    Chemical Substances Granulocyte Colony-Stimulating Factor (143011-72-7)
    Language English
    Publishing date 2011-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20110132
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Tonic Signaling and Its Effects on Lymphopoiesis of CAR-Armed Hematopoietic Stem and Progenitor Cells.

    Albert, Susann / Koristka, Stefanie / Gerbaulet, Alexander / Cartellieri, Marc / Arndt, Claudia / Feldmann, Anja / Berndt, Nicole / Loureiro, Liliana R / von Bonin, Malte / Ehninger, Gerhard / Eugster, Anne / Bonifacio, Ezio / Bornhäuser, Martin / Bachmann, Michael P / Ehninger, Armin

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Volume 202, Issue 6, Page(s) 1735–1746

    Abstract: Long-term survival of adoptively transferred chimeric Ag receptor (CAR) T cells is often limited. Transplantation of hematopoietic stem cells (HSCs) transduced to express CARs could help to overcome this problem as CAR-armed HSCs can continuously deliver ...

    Abstract Long-term survival of adoptively transferred chimeric Ag receptor (CAR) T cells is often limited. Transplantation of hematopoietic stem cells (HSCs) transduced to express CARs could help to overcome this problem as CAR-armed HSCs can continuously deliver CAR
    MeSH term(s) Adoptive Transfer ; Animals ; Cell Differentiation/physiology ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/metabolism ; Humans ; Lymphocyte Activation/physiology ; Lymphopoiesis/physiology ; Mice ; Mice, Inbred C57BL ; Receptors, Chimeric Antigen/metabolism ; Signal Transduction/physiology
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2019-02-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1801004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Anti-CAR-engineered T cells for epitope-based elimination of autologous CAR T cells.

    Koristka, Stefanie / Ziller-Walter, Pauline / Bergmann, Ralf / Arndt, Claudia / Feldmann, Anja / Kegler, Alexandra / Cartellieri, Marc / Ehninger, Armin / Ehninger, Gerhard / Bornhäuser, Martin / Bachmann, Michael P

    Cancer immunology, immunotherapy : CII

    2019  Volume 68, Issue 9, Page(s) 1401–1415

    Abstract: Although CAR T-cell therapy has demonstrated tremendous clinical efficacy especially in hematological malignancies, severe treatment-associated toxicities still compromise the widespread application of this innovative technology. Therefore, developing ... ...

    Abstract Although CAR T-cell therapy has demonstrated tremendous clinical efficacy especially in hematological malignancies, severe treatment-associated toxicities still compromise the widespread application of this innovative technology. Therefore, developing novel approaches to abrogate CAR T-cell-mediated side effects is of great relevance. Several promising strategies pursue the selective antibody-based depletion of adoptively transferred T cells via elimination markers. However, given the limited half-life and tissue penetration, dependence on the patients' immune system and on-target/off-side effects of proposed monoclonal antibodies, we sought to exploit αCAR-engineered T cells to efficiently eliminate CAR T cells. For comprehensive and specific recognition, a small peptide epitope (E-tag) was incorporated into the extracellular spacer region of CAR constructs. We provide first proof-of-concept for targeting this epitope by αE-tag CAR T cells, allowing an effective killing of autologous E-tagged CAR T cells both in vitro and in vivo whilst sparing cells lacking the E-tag. In addition to CAR T-cell cytotoxicity, the αE-tag-specific T cells can be empowered with cancer-fighting ability in case of relapse, hence, have versatile utility. Our proposed methodology can most probably be implemented in CAR T-cell therapies regardless of the targeted tumor antigen aiding in improving overall safety and survival control of highly potent gene-modified cells.
    MeSH term(s) Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Autoantigens/immunology ; Cytotoxicity, Immunologic ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/immunology ; Genetic Engineering ; Humans ; Immunotherapy, Adoptive/methods ; Male ; Mice ; Neoplasm Recurrence, Local ; PC-3 Cells ; Peptide Fragments/genetics ; Prostatic Neoplasms/immunology ; Prostatic Neoplasms/therapy ; Receptors, Antigen, T-Cell/genetics ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes, Cytotoxic/immunology ; Xenograft Model Antitumor Assays
    Chemical Substances Antigens, Neoplasm ; Autoantigens ; Epitopes, T-Lymphocyte ; Peptide Fragments ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2019-08-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-019-02376-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Exploratory investigation of PSCA-protein expression in primary breast cancer patients reveals a link to HER2/neu overexpression.

    Link, Theresa / Kuithan, Friederike / Ehninger, Armin / Kuhlmann, Jan Dominik / Kramer, Michael / Werner, Andreas / Gatzweiler, Axel / Richter, Barbara / Ehninger, Gerhard / Baretton, Gustavo / Bachmann, Michael / Wimberger, Pauline / Friedrich, Katrin

    Oncotarget

    2017  Volume 8, Issue 33, Page(s) 54592–54603

    Abstract: Background: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the ... ...

    Abstract Background: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study.
    Methods: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays.
    Results: PSCA-expression was detected in 94/405 patients (23%) and correlated with unfavorable histopathological grade (p=0.011) and increased Ki67 proliferation index (p=0.006). We observed a strong positive correlation between PSCA-protein expression and HER2/neu receptor status (p<0.001). PSCA did not provide prognostic information in the analyzed cohort. Interestingly, the distribution of PSCA-expression among triple negative patients was comparable to the total population.
    Conclusion: We identified a subgroup of PSCA-positive breast cancer patients, which could be amenable for a PSCA-targeted therapy. Moreover, given that we found a strong positive correlation between PSCA- and HER/neu expression, targeting PSCA may provide an alternative therapeutic option in case of trastuzumab resistance.
    Language English
    Publishing date 2017-08-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.17523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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