Article
Biotechnology & Applied Microbiology
Kurt Berckmueller, Justin Thomas, Eman A. Taha, Seunga Choo, Ravishankar Madhu, Greta Kanestrom, Peter B. Rupert, Roland Strong, Hans-Peter Kiem, Stefan Radtke
Summary: Novel HSC-targeted viral vectors have been developed that can specifically transduce CD90-expressing HSCs, and are expected to have significant potential in ex vivo gene therapy.
Article
Medicine, Research & Experimental
Nicole Cordes, Carolin Kolbe, Dominik Lock, Tatjana Holzer, Deborah Althoff, Daniel Schaefer, Franziska Blaeschke, Bettina Kotter, Sandra Karitzky, Claudia Rossig, Toni Cathomen, Tobias Feuchtinger, Iris Buerger, Mario Assenmacher, Thomas Schaser, Andrew D. Kaiser
Summary: A study found a rare type of relapse in treating B cell acute lymphoblastic leukemia patients with CAR-T cells, possibly caused by unintentional transduction of CAR-B cells. The study showed that LVs displaying anti-CD19 CARs had higher transduction efficacy due to specific binding with the respective antigen. Findings suggest the importance of safer manufacturing procedures to reduce the risk of this rare type of relapse in the future.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Computer Science, Cybernetics
Thomas Lindgren, Vaike Fors, Sarah Pink
Summary: This article explores the relationship between humans and autonomous driving vehicles using a longitudinal design ethnography method, incorporating theories of socio-materiality and entanglement, while identifying anticipatory experiences that arise from these relationships and their implications for informing UX design.
INTERNATIONAL JOURNAL OF HUMAN-COMPUTER INTERACTION
(2022)
Article
Engineering, Civil
Amolika Sinha, Daniel Bassil, Sai Chand, Navreet Virdi, Vinayak Dixit
Summary: The study investigates the impact of connected automated buses in a mixed fleet with connected automated vehicles on the performance of urban transport systems. Results show that connected automated buses can significantly reduce travel time and standstill times, while also decreasing forced lane changes between vehicles and improving road safety.
IEEE TRANSACTIONS ON INTELLIGENT TRANSPORTATION SYSTEMS
(2022)
Article
Biology
George B. Garside, Madeline Sandoval, Slobodan Beronja, K. Lenhard Rudolph
Summary: This study developed a novel technique for in vivo targeting of intestinal stem cells in the unperturbed intestinal epithelium across different regions of the intestine. This method enables in vivo somatic gene editing and genetic screening, which can speed up discoveries and mechanistic understanding of genetic pathways controlling the biology of the intestinal epithelium.
Article
Biotechnology & Applied Microbiology
Kevin Collon, Matthew C. Gallo, Jennifer A. Bell, Stephanie W. Chang, John Croom Sueiro Rodman, Osamu Sugiyama, Donald B. Kohn, Jay R. Lieberman
Summary: This study investigated the enhancement of lentiviral transduction of adipose-derived MSCs using LentiBOOST and protamine sulfate, finding that this combination could yield superior transduction efficiency compared to polybrene, without adverse effects on cell characteristics.
HUMAN GENE THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Zhen Zhang, Amy E. E. Baxter, Diqiu Ren, Kunhua Qin, Zeyu Chen, Sierra M. M. Collins, Hua Huang, Chad A. A. Komar, Peter F. F. Bailer, Jared B. B. Parker, Gerd A. A. Blobel, Rahul M. M. Kohli, E. John Wherry, Shelley L. L. Berger, Junwei Shi
Summary: Peptide-assisted genome editing allows efficient editing of single and multiple genes in hematopoietic cells. This system enables simple and well-tolerated delivery of CRISPR-Cas system into primary cells with minimal toxicity. It achieves rapid and robust genome editing in primary cells, including T cells and hematopoietic progenitor cells, with editing efficiencies exceeding 98%. The Peptide-Assisted Genome Editing (PAGE) provides a versatile platform for next-generation genome engineering in primary cells.
NATURE BIOTECHNOLOGY
(2023)
Article
Oncology
Maria Tristan-Manzano, Noelia Maldonado-Perez, Pedro Justicia-Lirio, Pilar Munoz, Marina Cortijo-Gutierrez, Kristina Pavlovic, Rosario Jimenez-Moreno, Sonia Nogueras, M. Dolores Carmona, Sabina Sanchez-Hernandez, Araceli Aguilar-Gonzalez, Maria Castella, Manel Juan, Concepcion Maranon, Juan Antonio Marchal, Karim Benabdellah, Concha Herrera, Francisco Martin
Summary: CAR-T cells generated using AW-LVs show improved efficacy and reduced side effects, making them a potential candidate for large-scale production of CAR-T products.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Oncology
Justin T. Huckaby, Elisa Landoni, Timothy M. Jacobs, Barbara Savoldo, Gianpietro Dotti, Samuel K. Lai
Summary: The study demonstrates the in vivo engineering of CAR-T cells using a redirected lentiviral system that offers exceptional specificity and efficiency in controlling the growth of aggressive B cell tumors, highlighting the promising approach for personalized cancer immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
David W. Scott
Summary: The use of CAR transduced T cells and engineered Tregs with specific receptors show great promise in cancer immunotherapy. Methods involving retroviral transduction of specific T-cell receptors, scFv, or antigens for various diseases models are discussed for their potential clinical translation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Dominik Lock, Razieh Monjezi, Caroline Brandes, Stephan Bates, Simon Lennartz, Karin Teppert, Leon Gehrke, Rafailla Karasakalidou-Seidt, Teodora Lukic, Marco Schmeer, Martin Schleef, Niels Werchau, Matthias Eyrich, Mario Assenmacher, Andrew Kaiser, Sabrina Prommersberger, Thomas Schaser, Michael Hudecek
Summary: We established an automated manufacturing process for CAR T cells using the CliniMACS Prodigy platform, which is scaled to provide therapeutic doses and achieves gene-transfer with virus-free Sleeping Beauty transposition.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Cell Biology
Priyanka S. Rana, David C. Soler, Jeries Kort, James J. Driscoll
Summary: Multiple myeloma is a lethal hematologic cancer characterized by the expansion of transformed plasma cells. TGF-beta signaling affects immune cell effectors and inhibiting this pathway can enhance immunotherapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Psychology, Applied
Esko Lehtonen, Fanny Malin, Tyron Louw, Yee Mun Lee, Teemu Itkonen, Satu Innamaa
Summary: This study found that conditionally automated cars have substantial potential to increase car travel once they become available. Willingness to perform leisure activities during automated driving, experienced usefulness of the system, and unmet travel needs were the main contributors to expecting to travel more by AV.
TRANSPORTATION RESEARCH PART F-TRAFFIC PSYCHOLOGY AND BEHAVIOUR
(2022)
Article
Chemistry, Multidisciplinary
Filippos T. Charitidis, Elham Adabi, Naphang Ho, Angela H. Braun, Ciara Tierney, Lisa Strasser, Frederic B. Thalheimer, Liam Childs, Jonathan Bones, Colin Clarke, Christian J. Buchholz
Summary: Lentiviral vectors (LV) have become an important tool for stable gene transfer. However, there is still room for improvement, especially in the selective delivery of genes to T cell subtypes. Whole transcriptome analyses on human T lymphocytes exposed to different LVs revealed upregulation of genes related to quiescence and antiviral restriction in CAR-negative cells. Rapamycin was found to enhance transduction rates without compromising CAR T cell activities, especially for CD8-LV and CD4-LV. Humanized mice experiments also showed improved in vivo CAR T cell generation and tumor control with CD8-LV, but further optimization of rapamycin administration schedule is needed.
Article
Medicine, Research & Experimental
Dongxin Wang, Qungang Zhou, Xiang Qiu, Xiaomei Liu, Chun Zhang
Summary: This study optimized the protocol for rAAV6 transduction of primary T cells, significantly improved the expression efficiency of the rAAV6 delivered CAR gene, and successfully generated rAAV6-based CAR-T cells (AAV-CAR-T). The findings provide an efficient method for AAV transduction of T cells and an alternative way for the preparation of CAR-T cells.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Letter
Hematology
Giorgio Ottaviano, Susan Baird, Denise Bonney, Philip Connor, Michelle Cummins, Pamela Evans, Brenda Gibson, Rachel Hough, Danielle Ingham, Anne Kelly, Amrana Qureshi, Donna Lancaster, John Moppett, Alice Norton, Jeanette Payne, Simone Stockley, Sara Ghorashian, Persis Amrolia, Waseem Qasim, Ajay Vora
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Dermatology
Vignesh Jayarajan, Evangelia Kounatidou, Waseem Qasim, Wei-Li Di
Summary: Genetic skin diseases, though rare, are severe and currently lack curative treatments. Ex vivo gene modification therapy holds promise for treating these conditions by correcting mutant genes in patients' cells.
EXPERIMENTAL DERMATOLOGY
(2021)
Article
Oncology
Christos Georgiadis, Jane Rasaiyaah, Soragia Athina Gkazi, Roland Preece, Aniekan Etuk, Abraham Christi, Waseem Qasim
Summary: The use of base editing technology allows for the generation of CAR T cells with resistance to T cell fratricide, enabling enhanced cytotoxic effects against specific targets. Co-cultured 3CAR and 7CAR cells exhibit high cytotoxicity, particularly effective against CD3 + CD7 + T-ALL targets.
Article
Multidisciplinary Sciences
Ioanna A. Rota, Adam E. Handel, Stefano Maio, Fabian Klein, Fatima Dhalla, Mary E. Deadman, Stanley Cheuk, Joseph A. Newman, Yale S. Michaels, Saulius Zuklys, Nicolas Prevot, Philip Hublitz, Philip D. Charles, Athina Soragia Gkazi, Eleni Adamopoulou, Waseem Qasim, Edward Graham Davies, Imelda Hanson, Alistair T. Pagnamenta, Carme Camps, Helene M. Dreau, Andrea White, Kieran James, Roman Fischer, Opher Gileadi, Jenny C. Taylor, Tudor Fulga, B. Christoffer Lagerholm, Graham Anderson, Erdinc Sezgin, Georg A. Hollaender
Summary: The transcription factor FOXN1 plays a crucial role in thymic epithelial cell development and function, with its expression being differentially regulated during organogenesis. It forms multimolecular nuclear condensates important for transcriptional activity, where the C-terminal sequence regulates diffusion velocity and binding to gene regulatory regions. Mutant FOXN1 with modified C-terminal sequence is transcriptionally inactive and acts as a dominant negative factor, causing athymia and severe lymphopenia. This gain-of-function mutant disrupts TEC differentiation in mice, showing gene dose dependency for specific TEC subtypes.
Article
Oncology
Giorgio Ottaviano, Waseem Qasim
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
(2022)
Review
Hematology
Waseem Qasim
Summary: Genome editing technologies, such as CRISPR/Cas9, are being used to overcome the challenges of allogeneic T-cell therapy for blood malignancies by disrupting TCR alpha beta and preventing graft-versus-host disease. Premanufactured banks of allogeneic donor-derived CAR T cells could help address the complex logistics and high costs of autologous therapies, if HLA-mismatched T-cell therapy can be successfully addressed. Clinical trials will be crucial in determining the safety and efficacy of these modified T-cell therapies.
Meeting Abstract
Hematology
Arnold Kloos, Christos Georgiadis, Annie Etuk, Soragia Athina Gkazi, Farhatullah Syed, Toni Braybrook, Hong Zhan, Renuka Kadirkamanathan, Nadine Kattre, Kerstin Goerlich, Thomas Fangmann, Axel Schambach, Martin G. Sauer, Michael Heuser, Waseem Qasim
Review
Biotechnology & Applied Microbiology
Chiara Bonini, Aude G. Chapuis, Michael Hudecek, Sonia Guedan, Chiara Magnani, Waseem Qasim
Summary: Gene editing technologies can address challenges in adoptive cellular therapy, such as therapy resistance, immune reactions, and immunosuppressive signals. These innovative approaches improve the efficacy and safety of cellular therapy, benefiting more patients.
HUMAN GENE THERAPY
(2023)
Meeting Abstract
Biotechnology & Applied Microbiology
A. Etuk, C. Georgiadis, R. Preece, W. Qasim
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
C. Georgiadis, G. Ottaviano, S. A. Gkazi, F. Syed, H. Zhan, A. Etuk, R. Preece, W. Qasim
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
O. Gough, R. Preece, H. Aldahshan, C. Georgiadis, W. Qasim
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
R. Kadirkamanathan, C. Georgiadis, A. Etuk, T. Braybrook, R. Preece, H. Zhan, W. Qasim
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
H. Aldahshan, R. Preece, H. Brezovjakova, C. Georgiadis, W. Qasim
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
H. Brezovjakova, V. Jayarajan, O. Gough, A. Etuk, A. Petrova, W. L. Di, W. Qasim
HUMAN GENE THERAPY
(2022)
Article
Immunology
Su Han Lum, Reem Elfeky, Federica R. Achini, Adriana Margarit-Soler, Bianca Cinicola, Inigo Perez-Heras, Zohreh Nademi, Terry Flood, Tim Cheetham, Austen Worth, Waseem Qasim, Rakesh Amin, Kanchan Rao, Robert Chiesa, Robbert G. M. Bredius, Persis Amrolia, Mario Abinun, Sophie Hambleton, Paul Veys, Andrew R. Gennery, Arjan Lankester, Mary Slatter
Summary: This multicenter retrospective study investigated the occurrence of post-HCT autoimmune diseases in 596 children with PID. The study found that the incidence of post-HCT AD was 11% at 8 years post-HCT, with a median onset time of 2.2 years. Older age at transplant and T cell-depleted graft were significant predictors of post-HCT AD.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
