Review
Immunology
Peng Zhang, Yang Zhang, Nan Ji
Summary: Glioblastoma (GBM) is a deadly brain cancer with limited efficacy of standard treatments, necessitating the development of new therapies. Chimeric antigen receptor T (CAR-T) cell immunotherapy has shown success in hematological malignancies, but has not yet yielded promising results in GBM. CAR-T cell therapy for GBM faces challenges including tumor heterogeneity, immunosuppressive microenvironment, and cell persistence.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sophia Stock, Anna-Kristina Kluever, Stefan Endres, Sebastian Kobold
Summary: Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in treating specific hematological malignancies. However, many patients do not respond or relapse after treatment. Strategies such as combining CAR T cells with other treatments and using clinically approved compounds have been investigated to improve this therapy.
Review
Oncology
Sophia Stock, Anna-Kristina Kluever, Luisa Fertig, Vivien D. Menkhoff, Marion Subklewe, Stefan Endres, Sebastian Kobold
Summary: The clinical application of CAR T-cell therapy has revolutionized the treatment options for certain terminally ill patients with blood-borne cancers. However, the therapy can lead to severe toxicities, and efforts are being made to better control CAR T-cell activity and manage its associated side effects through various strategies and mechanisms.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Clinical Neurology
Lisa Feldman, Christine Brown, Behnam Badie
Summary: CAR T-cell therapy, utilizing genetically engineered cells from patients to target tumor cells, has emerged as a promising strategy for treating GBM. Ongoing clinical trials are exploring the potential of this approach to combat the challenges associated with GBM treatment.
Review
Oncology
Mahasha P. J. Perera, Patrick B. Thomas, Gail P. Risbridger, Renea Taylor, Arun Azad, Michael S. Hofman, Elizabeth D. Williams, Ian Vela
Summary: This review discusses the role of CAR-T cell therapy in men with metastatic castrate-resistant prostate cancer. Prostate cancer is the most commonly diagnosed solid-organ cancer in males worldwide. Men with metastatic castrate-resistant prostate cancer have limited treatment options, and current therapies are not curative. CAR-T cell therapy has shown success in the treatment of treatment-resistant hematological malignancies, and there are ongoing studies investigating its utility in solid tumors. However, preliminary clinical trials in men with prostate cancer have had limited efficacy, indicating the need for further research to enhance understanding and translation of this therapy.
Article
Immunology
Rui Zheng, Yuankun Chen, Yiting Zhang, Sixin Liang, Xiaojuan Zhao, Yiyi Wang, Pengju Wang, Ruotong Meng, Angang Yang, Bo Yan
Summary: Our study explores the effect of low-affinity CARs using humanized scFvs on the function of CAR-T cells. We find that moderately reducing the affinity of CARs can maintain anti-tumor efficacy and improve the safety of CAR therapy both in vitro and in vivo. In addition, T cells expressing the VL domain only antibody show long-lasting tumor elimination capability and lower cytokine levels.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Medicine, Research & Experimental
Yuxi Luo, Guiqin Song, Shichu Liang, Feifei Li, Kang Liu
Summary: CAR-modified T-cells, a novel cancer immunotherapy, target specific surface antigens on tumor cells through genetic engineering. While showing notable efficacy in hematological tumor treatment, challenges exist in treating solid tumors, along with specific side effects associated with CAR T-cell therapy.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Multidisciplinary Sciences
Mario Bunse, Janina Pfeilschifter, Julia Bluhm, Maria Zschummel, Jara J. Joedicke, Anthea Wirges, Helen Stark, Vivien Kretschmer, Markus Chmielewski, Wolfgang Uckert, Hinrich Abken, Joerg Westermann, Armin Rehm, Uta E. Hoepken
Summary: The study demonstrates that CAR-T cells targeting CXCR5 effectively inhibit tumor growth by depleting both B cells and follicular T helper cells in lymphoma models, suggesting a promising treatment strategy for nodal B-NHLs.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Nattaporn Phanthaphol, Chalermchai Somboonpatarakun, Kwanpirom Suwanchiwasiri, Thaweesak Chieochansin, Jatuporn Sujjitjoon, Sopit Wongkham, John Maher, Mutita Junking, Pa-thai Yenchitsomanus
Summary: CAR T cell therapy has shown efficacy in hematologic malignancies, but further investigation is needed for its application in solid tumors. The selection of target antigens highly expressed in cancer cells but not normal cells is crucial for successful immunotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, Fatemeh Rahbarizadeh
Summary: CAR-T therapy has shown remarkable success in treating B-ALL, but faces challenges such as adverse events and immune-related issues. Advances in media design and other factors may lead to more effective therapy in the future.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Zixun Yin, Ya Zhang, Xin Wang
Summary: B-cell non-Hodgkin lymphoma is a heterogeneous disease that remains incurable, necessitating the development of novel therapies. CAR-T cell therapy shows promising potential in refractory or relapsed B-NHL, but comes with adverse effects. New antigen-targeted CAR-T products and four-generation CAR-T are rapidly developing to overcome these limitations.
BIOMARKER RESEARCH
(2021)
Review
Hematology
Jan Koedam, Martin Wermke, Armin Ehninger, Marc Cartellieri, Gerhard Ehninger
Summary: The treatment outcome for relapsed or refractory AML patients is poor, prompting the need for new treatment options. CAR-T cell therapy is being explored as a potential approach, with several interesting AML targets under investigation. Initial clinical data has shown mixed results, highlighting the need for further research. Strategies to enhance control and reduce toxicity of CAR-T cells are being studied.
CURRENT OPINION IN HEMATOLOGY
(2022)
Article
Hematology
Paolo Strati, Sairah Ahmed, Fateeha Furqan, Luis E. Fayad, Hun J. Lee, Swaminathan P. Iyer, Ranjit Nair, Loretta J. Nastoupil, Simrit Parmar, Maria A. Rodriguez, Felipe Samaniego, Raphael E. Steiner, Michael Wang, Chelsea C. Pinnix, Sandra B. Horowitz, Lei Feng, Ryan Sun, Catherine M. Claussen, Misha C. Hawkins, Nicole A. Johnson, Prachee Singh, Haleigh Mistry, Swapna Johncy, Sherry Adkins, Partow Kebriaei, Elizabeth J. Shpall, Michael R. Green, Christopher R. Flowers, Jason Westin, Sattva S. Neelapu
Summary: For patients with relapsed or refractory large B-cell lymphoma undergoing CAR T-cell therapy, the use of corticosteroids for toxicity management may impact clinical outcomes. Higher cumulative dose, prolonged duration, and early initiation of corticosteroids were associated with shorter progression-free and overall survival.
Article
Immunology
Bilge Debelec-Butuner, Oliver Quitt, Sophia Schreiber, Frank Momburg, Karin Wisskirchen, Ulrike Protzer
Summary: Despite the availability of a prophylactic vaccine, many people still die from hepatitis B virus (HBV)-related liver disease. Current antiviral therapies are not curative, so new strategies are urgently needed. This study explores the use of bi- and trispecific T-cell engager antibodies as an alternative treatment for HBV.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jingting Min, Chirong Long, Lu Zhang, Jiakang Duan, Honglian Fan, Fei Chu, Zhenghong Li
Summary: Non-small cell lung cancer (NSCLC) is a prevalent and fatal malignancy, and CAR-T cell therapy targeting c-Met shows potential as a therapeutic strategy. In vitro and in vivo experiments demonstrated that c-Met CAR-T cells exhibit enhanced cytotoxicity against NSCLC cells.
Article
Immunology
Maarten A. Ligtenberg, Dimitrios Mougiakakos, Madhura Mukhopadhyay, Kristina Witt, Alvaro Lladser, Markus Chmielewski, Tobias Riet, Hinrich Abken, Rolf Kiessling
JOURNAL OF IMMUNOLOGY
(2016)
Article
Cardiac & Cardiovascular Systems
Peter L. Haldenwang, Tobias Klein, Klaus Neef, Tobias Riet, Anja Sterner-Kock, Hildegard Christ, Thorsten Wahlers, Justus T. Strauch
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2012)
Article
Biotechnology & Applied Microbiology
David M. Kofler, Markus Chmielewski, Gunter Rappl, Anja Hombach, Tobias Riet, Annette Schmidt, Andreas A. Hombach, Clemens-Martin Wendtner, Hinrich Abken
Article
Multidisciplinary Sciences
Gunter Rappl, Tobias Riet, Sabine Awerkiew, Annette Schmidt, Andreas A. Hombach, Herbert Pfister, Hinrich Abken
Review
Immunology
Tobias Riet, Markus Chmielewski
Summary: CAR T-cell therapy has revolutionized oncology and holds potential for treating autoimmune diseases. The development of antigen-specific receptors through genetic engineering of regulatory T cells (Tregs) is a logical step to improve their therapeutic potency. Preclinical studies have shown promising immune modulating properties of CAR Tregs in mouse models, but concerns remain regarding target selectivity, suppressive functions, phenotype stability, and safety aspects.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Jakob Kremer, Pierre Henschel, Daniel Simon, Tobias Riet, Christine Falk, Matthias Hardtke-Wolenski, Heiner Wedemeyer, Fatih Noyan, Elmar Jaeckel
Summary: The study demonstrated that enhancing the function and stability of CAR-Tregs through membrane-associated IL-2 expression is effective. The results showed that these cells are more stable under inflammatory conditions, survive better in the Treg niche, and are resistant to CNI therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Tom Pieper, Kristian Daniel Ralph Roth, Viktor Glaser, Tobias Riet, Laura Elisa Buitrago-Molina, Maike Hagedorn, Maren Lieber, Michael Hust, Fatih Noyan, Elmar Jaeckel, Matthias Hardtke-Wolenski
Summary: Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in treating autoimmune diseases. However, obtaining sufficient antigen-specific Tregs from patients with autoimmune disorders remains challenging. In this study, researchers aimed to generate CARs against TSPAN7, a membrane protein highly expressed on the surface of pancreatic beta cells, using phage display technology. Although the resulting CARs were functional and specifically activated by the target structure, they could not recognize TSPAN7 on the surface of beta cells. This study demonstrates the power of CAR technology in generating antigen-specific T cells and provides new approaches for functional CAR generation.
Article
Immunology
Pierre Henschel, Sybille Landwehr-Kenzel, Niklas Engels, Andrea Schienke, Jakob Kremer, Tobias Riet, Nella Redel, Konstantinos Iordanidis, Valerie Saetzler, Katharina John, Miriam Heider, Matthias Hardtke-Wolenski, Heiner Wedemeyer, Elmar Jaeckel, Fatih Noyan
Summary: Researchers have developed an HLA-A2specific CAR vector that co-expresses FOXP3, which can increase the safety and efficacy of CAR-Treg products. Stable expression of FOXP3 in Tregs prevents conversion into pathogenic T effector cells under pro-inflammatory conditions.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Cell Biology
Valerie Saetzler, Tobias Riet, Andrea Schienke, Pierre Henschel, Kiara Freitag, Alexander Haake, Frank L. Heppner, Laura Elisa Buitrago-Molina, Fatih Noyan, Elmar Jaeckel, Matthias Hardtke-Wolenski
Summary: In this study, a chimeric antigen receptor (CAR) targeting beta-amyloid was generated using an antibody-like single-chain variable fragment from a phage library. The obtained CAR-Tregs showed antigen-specific activation and suppressive capacity. This study highlights the potential of CAR technology in generating antigen-specific Tregs and provides novel approaches for developing functional CARs.
Article
Oncology
Ruth Fluemann, Julia Hansen, Benedikt W. Pelzer, Pascal Nieper, Tim Lohmann, Ilmars Kisis, Tobias Riet, Viktoria Kohlhas, Phuong-Hien Nguyen, Martin Peifer, Nima Abedpour, Graziella Bosco, Roman K. Thomas, Moritz Kochanek, Jacqueline Knufer, Lorenz Jonigkeit, Filippo Beleggia, Alessandra Holzem, Reinhard Buttner, Philipp Lohneis, Jorn Meinel, Monika Ortmann, Thorsten Persigehl, Michael Hallek, Dinis Pedro Calado, Markus Chmielewski, Sebastian Klein, Joachim R. Goethert, Bjoern Chapuy, Branko Zevnik, F. Thomas Wunderlich, Bastian von Tresckow, Ron D. Jachimowicz, Ari M. Melnick, Hans Christian Reinhardt, Gero Knittel
Summary: Genomic profiling identified 5 subtypes of DLBCL, including the MCD/C5 cluster with MYD88, BCL2, PRDM1, and/or SPIB aberrations. Mouse models with B cell-specific Prdm1 or Spib aberrations were generated, showing molecular features of prememory and light-zone B cells. Combined BTK/BCL2 inhibition exhibited therapeutic activity in both mouse models and relapsed/refractory DLBCL patients.
BLOOD CANCER DISCOVERY
(2023)
Meeting Abstract
Hematology
David M. Kofler, Markus Chmielewski, Tobias Riet, Andreas Hombach, Michael Hallek, Clemens M. Wendtner, Hinrich Abken
Meeting Abstract
Hematology
David M. Kofler, Markus Chmielewski, Heike Koehler, Tobias Riet, Patrick Schmidt, Gunter Rappl, Andreas Hombach, Michael Hallek, Clemens M. Wendtner, Hinrich Abken
