Article
Virology
Valeria Morante, Martina Borghi, Iole Farina, Zuleika Michelini, Felicia Grasso, Alessandra Gallinaro, Serena Cecchetti, Antonio Di Virgilio, Andrea Canitano, Maria Franca Pirillo, Roberta Bona, Andrea Cara, Donatella Negri
Summary: The study validated the efficacy of the vaccine platform based on IDLVs for cancer immunotherapy in preclinical murine models, demonstrating the ability to eradicate and control tumor growth by delivering antigens such as OVA and TRP2.
Article
Biochemistry & Molecular Biology
Shiran Shapira, Eynat Finkelshtein, Dina Kazanov, Esmira Naftali, Irena Stepansky, Abraham Loyter, Daniel Elbirt, Mori Hay-Levy, Eli Brazowski, Faina Bedny, Roy Dekel, Dov Hershkovitz, Arye Blachar, Ido Wolf, Nadir Arber
Summary: A novel targeted cancer therapeutic platform based on lentiviral integrase stimulated by integrase-derived peptides specifically delivered to cancer cells via CD24 antigen-antibody targeting is proposed. The platform leads to apoptosis in tumor cells by inducing genomic instability, presenting a potentially effective and safe approach for selective cancer cell eradication.
Article
Virology
Sneha Mahesh, Jenny Li, Tatianna Travieso, Danai Psaradelli, Donatella Negri, Mary Klotman, Andrea Cara, Maria Blasi
Summary: The choice of vector promoter influences antigen expression levels in target cells and the magnitude of T cell responses in vivo.
Article
Biology
Min Wen Ku, Pierre Authie, Fabien Nevo, Philippe Souque, Maryline Bourgine, Marta Romano, Pierre Charneau, Laleh Majlessi
Summary: Utilizing a lentiviral vector system with a human beta 2-microglobulin promoter, researchers found that the lentiviral-based vaccine outperformed the Ad5 'gold-standard' in mice and rats by inducing a polyfunctional and long-lived immune response.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Pavel Spirin, Elena Shyrokova, Valeria Vedernikova, Timofey Lebedev, Vladimir Prassolov
Summary: Chloroquine and Emetine, drugs used to treat parasitic infections in humans, have been shown to have antiviral and anticancer effects. When combined with lentiviral particles, these drugs synergistically suppress the growth of cancer cells.
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.
Review
Pharmacology & Pharmacy
Kirill Nemirov, Maryline Bourgine, Francois Anna, Yu Wei, Pierre Charneau, Laleh Majlessi
Summary: Lentiviral vectors are highly effective for vaccination, especially in transducing dendritic cells and activating naive T cells. They induce endogenous expression of transgenic antigens and stimulate strong and long-lasting immunity. Lentiviral vectors have low pro-inflammatory properties and can be used for mucosal vaccination. This review summarizes the immunological aspects, optimization for CD4(+) T cell induction, and recent data on lentiviral vector-based vaccination in preclinical models for various infectious diseases including flaviviruses, SARS-CoV-2, and Mycobacterium tuberculosis.
Article
Cell Biology
Yi-Chang Wang, Andrew A. Kelso, Adak Karamafrooz, Yi-Hsuan Chen, Wei-Kai Chen, Chun-Ting Cheng, Yue Qi, Long Gu, Linda Malkas, Angelo Taglialatela, Hsing-Jien Kung, George-Lucian Moldovan, Alberto Ciccia, Jeremy M. Stark, David K. Ann
Summary: The dependence of cancer cells on arginine creates a vulnerability in metabolism. This study investigates how the availability of arginine affects DNA replication and resistance to genotoxicity. Through DNA combing assays, it is found that limiting extracellular arginine leads to the arrest of cancer cells and a slowdown in DNA replication. The translation of new histone H4 is arginine-dependent and influences DNA replication. Increased PCNA occupancy and HLTF-catalyzed PCNA K63-linked polyubiquitination protect arginine-starved cells from DNA damage. Arginine-deprived cancer cells display tolerance to genotoxicity in a PCNA K63-linked polyubiquitination-dependent manner. These findings emphasize the crucial role of extracellular arginine in nutrient-regulated DNA replication and provide potential avenues for cancer treatment development.
Article
Immunology
Alessandra Gallinaro, Maria Franca Pirillo, Yoann Aldon, Serena Cecchetti, Zuleika Michelini, Antonella Tinari, Martina Borghi, Andrea Canitano, Paul F. McKay, Roberta Bona, Maria Fenicia Vescio, Felicia Grasso, Maria Blasi, Silvia Baroncelli, Gabriella Scarlatti, Celia LaBranche, David Montefiori, Mary E. Klotman, Rogier W. Sanders, Robin J. Shattock, Donatella Negri, Andrea Cara
Summary: This article discusses the development of an HIV-1 vaccine based on IDLV, demonstrating its ability to induce specific and persistent immune responses in mice and macaques, and showing that displaying stabilized trimeric Env can induce more sustained humoral responses.
Article
Medicine, Research & Experimental
Alexander Michels, Annika M. Frank, Dorothee M. Guenther, Mehryad Mataei, Kathleen Borner, Dirk Grimm, Jessica Hartmann, Christian J. Buchholz
Summary: This study successfully improved gene delivery efficiency to CD8+ mouse lymphocytes using mCD8-LV, based on DARPin binding to murine CD8. The results suggest a potential application of DARPins in AAV vectors for targeted gene therapy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Hematology
Julia H. Joo, Xuefeng Wang, Swati Singh, Chun -Yu Chen, Chong Li, Jennifer E. Adair, Hans -Peter Kiem, David J. Rawlings, Carol H. Miao
Summary: This study demonstrates the long-term safety and efficacy of intraosseous delivery of lentiviral vector for factor VIII in treating hemophilia A in a humanized model. The successful transduction of self-regenerating hematopoietic stem and progenitor cells was confirmed, indicating potential for long-term transgene expression. The study also evaluated the safety and efficacy of gene transfer therapy into human HSPCs, showing megakaryocyte-specific gene expression and polyclonal integration pattern. Overall, the results support the feasibility of translating this method for clinical applications.
Article
Immunology
Valerio Renna, Elena Surova, Ahmad Khadour, Moumita Datta, Timm Amendt, Elias Hobeika, Hassan Jumaa
Summary: This study found that different types of B cell receptors can regulate the activation threshold of B cells to meet their diverse requirements during development. IgM triggers editing of autoreactive specificities during early developmental stages, while IgD can ignore weakly interacting autoantigens while still responding to high-affinity antigens.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Oncology
Eva Sum, Moritz Rapp, Philipp Froebel, Marine Le Clech, Harald Durr, Anna Maria Giusti, Mario Perro, Dario Speziale, Leo Kunz, Elena Menietti, Peter Bruenker, Ulrike Hopfer, Martin Lechmann, Andrzej Sobieniecki, Birte Appelt, Roberto Adelfio, Valeria Nicolini, Anne Freimoser-Grundschober, Whitney Jordaan, Sara Labiano, Felix Weber, Thomas Emrich, Francois Christen, Birgit Essig, Pedro Romero, Christine Trumpfheller, Pablo Umana
Summary: FAP-CD40 specifically targets CD40 agonism to the tumor, enhancing anti-tumor immunity while reducing systemic toxicity. High doses of FAP-CD40 are essential for effective tumor regression and long-term protection, with well-tolerated side effects compared to non-targeted CD40 agonists.
CLINICAL CANCER RESEARCH
(2021)
Article
Immunology
Shin-Young Na, Gurumoorthy Krishnamoorthy
Summary: The study demonstrates that ectopic expression of MOG in immune organs can induce MOG-specific tolerance and long-lasting protection, potentially serving as a therapeutic strategy for specific autoantigen-driven autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Patrick Reichenbach, Greta Maria Paola Giordano Attianese, Khaoula Ouchen, Elisabetta Cribioli, Melanie Triboulet, Sarah Ash, Margaux Saillard, Romain Vuillefroy de Silly, George Coukos, Melita Irving
Summary: This study reports the design and production of a lentiviral vector that incorporates two functionally independent promoters, allowing for the expression of a tumour-directed receptor and inducible gene in T cells. The vector enables the delivery of various genes to human T cells, improving the safety and efficacy of T-cell therapies.
NATURE BIOMEDICAL ENGINEERING
(2023)
Review
Medicine, General & Internal
Alessio Cantore, Alessandro Fraldi, Vasco Meneghini, Angela Gritti
Summary: In vivo genetic engineering is a promising treatment method for various diseases, with viral vector-mediated gene transfer and genome/epigenome editing being the main approaches. This review explores the advanced in vivo gene therapies available and in development, and discusses the challenges and potential solutions, focusing on the nervous system and liver as examples.
FRONTIERS IN MEDICINE
(2022)
Article
Multidisciplinary Sciences
Michela Milani, Cesare Canepari, Tongyao Liu, Mauro Biffi, Fabio Russo, Tiziana Plati, Rosalia Curto, Susannah Patarroyo-White, Douglas Drager, Ilaria Visigalli, Chiara Brombin, Paola Albertini, Antonia Follenzi, Eduard Ayuso, Christian Mueller, Andrea Annoni, Luigi Naldini, Alessio Cantore
Summary: Liver gene therapy using lentiviral vectors that integrate into the host cell genome has shown efficient liver gene transfer in mice, dogs, and non-human primates. In this study, we compared engineered coagulation factor VIII transgenes and found that codon-usage optimization and inclusion of an unstructured XTEN peptide significantly increased factor VIII expression in mice and non-human primates. Stable and long-term normal or above-normal factor VIII activity was achieved in hemophilia A mouse models. This research opens up new possibilities for treating hemophilia A using lentiviral gene therapy.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Fabio Russo, Eliana Ruggiero, Rosalia Curto, Laura Passeri, Francesca Sanvito, Ileana Bortolomai, Anna Villa, Silvia Gregori, Andrea Annoni
Summary: The study developed a gene transfer approach to modify the T cell repertoire in thymic epithelial cells, correcting the autoimmune response in type 1 diabetes. The strategy involved intrathymic injection of a lentiviral vector to achieve stable transgene expression in thymic epithelial cells, leading to successful correction of the disease in mice models.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biotechnology & Applied Microbiology
Jaitip Tipanee, Ermira Samara-Kuko, Thierry Gevaert, Marinee K. Chuah, Thierry VandenDriessche
Summary: This study developed a non-viral platform based on Sleeping Beauty transposons and minicircles for genetic modification, allowing efficient expression of CD19-28z.CAR and inactivation of allogeneic TCRs using CRISPR-Cas9. The resulting CAR T cells showed anti-tumor activity against CD19+ tumor cells and induced complete tumor remission in a mouse model, while minimizing TCR alloreactivity and GvHD. This non-viral approach provides an alternative method for generating next-generation CD19-specific CAR T cells, reducing GvHD risk and manufacturing constraints associated with viral vectors.
Editorial Material
Biotechnology & Applied Microbiology
Thierry VandenDriessche, Steven W. Pipe, Glenn F. Pierce, Radoslaw Kaczmarek
Editorial Material
Biotechnology & Applied Microbiology
Thierry VandenDriessche, Marinee K. Chuah
Review
Biotechnology & Applied Microbiology
Dries De Wolf, Kshitiz Singh, Marinee K. Chuah, Thierry Vandendriessche
Summary: Extensive preclinical research has led to the recent regulatory approval of gene therapy products for hemophilia. Roctavian and Hemgenix have shown significant efficacy and safety in clinical trials, resulting in increased levels of clotting factors and reduced bleeding episodes for patients. However, there is variability in patient response and short-term liver inflammation was observed. Longer follow-up studies are needed to determine if lifelong expression of clotting factors can be achieved. Next-generation gene editing technologies offer new prospects for a sustained cure for hemophilia.
HUMAN GENE THERAPY
(2023)
Meeting Abstract
Biotechnology & Applied Microbiology
E. Barbon, C. Negri, A. Raimondi, A. Fabiano, F. Russo, G. la Marca, A. Cantore
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
C. Canepari, M. Milani, F. Russo, F. Starinieri, R. Norata, M. Rocchi, M. Biffi, A. Fabiano, F. Sanvito, A. Cantore
HUMAN GENE THERAPY
(2022)
Meeting Abstract
Biotechnology & Applied Microbiology
Michela Milani, Francesco Starinieri, Stefano Beretta, Tiziana Plati, Anna Fabiano, Cesare Canepari, Luigi Aloia, Fabio Russo, Mauro Biffi, Ivan Merelli, Meritxell Huch, Luigi Naldini, Alessio Cantore
Meeting Abstract
Biotechnology & Applied Microbiology
Susannah Patarroyo-White, Samantha Wilder, Douglas Drager, Alessio Cantore, Michela Milani, Andrea Annoni, Mauro Biffi, Luigi Naldini, Dinesh Bangari, Mostafa Kabiri, Michelle Potter, Tongyao Liu, Christian Mueller
Meeting Abstract
Biotechnology & Applied Microbiology
Francesco Starinieri, Michela Milani, Cesare Canepari, Chiara Simoni, Anna Fabiano, Tiziana Plati, Mauro Biffi, Fabio Russo, Eugenia Cammarota, Alessio Cantore
Meeting Abstract
Biotechnology & Applied Microbiology
Elena Barbon, Camilla Negri, Chiara Simoni, Anna Fabiano, Fabio Russo, Alessio Cantore
Meeting Abstract
Biotechnology & Applied Microbiology
Cesare Canepari, Michela Milani, Fabio Russo, Mauro Biffi, Anna Fabiano, Andrea Annoni, Alessio Cantore
Meeting Abstract
Biotechnology & Applied Microbiology
Naphang Ho, Shiwani Agarwal, Michela Milani, Alessio Cantore, Christian Buchholz, Frederic Thalheimer