Italy in Biotech

⚕️ 🇮🇹 Italy's Pharmaceutical Legacy: Family-Owned Enterprises Driving Innovation and Global Impact 🇮🇹 ⚕️ 💊 The Italian #pharmaceutical #industry is distinguished by its rich heritage and the enduring presence of family-owned enterprises. Many leading companies trace their origins back over a century, with for example MENARINI Group founded in 1886, Zambon in 1906, Angelini Industries in 1919, Bracco in 1927, Chiesi Group in 1935, and Dompé in 1940. This longstanding tradition of family ownership has fostered a deep commitment to long-term innovation and quality. Italian pharmaceutical companies have successfully navigated the evolving global pharmaceutical landscape, leveraging their heritage to drive advancements in healthcare. 💰 The #Italian pharmaceutical industry, indeed, stands as a pivotal player in Europe, showcasing remarkable growth and innovation. In 2023, Italy's pharmaceutical production value exceeded €52 billion, reinforcing its position among Europe's top producers. 📈 However, when compared to the United States, Europe—including Italy—faces #challenges in pharmaceutical innovation. The U.S. leads in life sciences investments, attracting significant talent and offering competitive salaries, which has resulted in a substantial investment gap between the U.S. and Europe. 🚀 Despite these challenges, Italian pharmaceutical companies are proactively investing in innovation. For instance, Chiesi Group has established Chiesi Ventures, focusing on respiratory, neonatology, and rare diseases. More recently, Angelini Industries launched Angelini Ventures with a record of €300 million to support innovations in the #biotech and life sciences sector. 🎯 These #strategic initiatives highlight Italy's commitment to advancing #healthcare solutions and bridging the innovation gap with global counterparts. The Italian pharma ecosystem continues to evolve, contributing significantly to both the #European and #global healthcare landscapes. 🔬 Their sustained success underscores the significant role that #familyowned enterprises play in the Italian pharmaceutical sector, contributing to its resilience and ongoing contributions to #innovation both in the European and global healthcare.

💡A Novel Dual targeting Strategy Shows Promise for Treating an Aggressive form of Melanoma 💡 🔬 Exciting work just published in Cell by Cell Press by Michelangelo Marasco, MD, PhD from the group of Sandra Misale and M. Neal Rosen, together with an exceptional team sheds light on a potential therapeutic breakthrough for NF1-null melanoma — a highly aggressive subtype with few targeted treatment options. 💊 The work by Marasco et al. explores a promising novel therapeutic strategy for treating NF1-null melanoma, a type of melanoma with limited targeted treatment options. #Neurofibromin (NF1) normally suppresses #RAS signaling, and its absence leads to uncontrolled RAS-MAPK pathway activation, which drives melanoma progression. 💉 By combining #MEK and #SOS1 inhibition, the team effectively suppresses ERK signaling, which halts tumor growth and induces cell death. Importantly, this approach avoids the toxicity associated with similar pathways, making it a promising avenue for #FutureTherapies. ⚕️ This research addresses a critical unmet medical need. NF1-null #melanomas have poor outcomes with current therapies, highlighting an urgent need for targeted options. Dual MEK-SOS1 inhibition could represent a viable and safer therapeutic strategy, with potential applications extending beyond melanoma to other cancers where NF1 is implicated. 👩🏻🔬 A special shoutout to Sandra Misale, an Italian scientist making significant strides abroad in oncology research. Her dedication and expertise are paving the way for innovation in cancer therapy. 👏 Congratulations to the entire team! Michelangelo Marasco, MD, PhD, Dinesh Kumar, Tessa Seale, Santiago Garcia Borrego, Esther Kaplun, Ilinca Aricescu, Soren Cole, Besnik Qeriqi, Juan Qiu, Xiaoping Chen, Amber Bahr, Deborah Fidele, Marco H. Hofmann, Daniel Gerlach, Fabio Savarese, Taha Merghoub, Jedd D. Wolchok, Zhan Yao, Elisa de Stanchina, David Solit, Sandra Misale and M. Neal Rosen and to their institutions: Memorial Sloan Kettering Cancer Center, The Johns Hopkins University.

🚀 Novel metabolic pathway that fuels immunotherapy resistance uncovered 🚀 🔬 Immunotherapy has transformed cancer treatment, yet a significant challenge remains: many cancers, especially aggressive types like pancreatic ductal adenocarcinoma, resist immunotherapy. 👨🏻🔬 In a recent groundbreaking study published in Nature Cancer, the research team led by the Italian Tommaso Scolaro, from the group of Massimiliano Mazzone and Baki Topal at KU Leuven and VIB, uncovered a metabolic pathway that fuels immunotherapy resistance. Congratulations on this impactful work! 🔍 Key Findings: 🧬 The study identified that cytidine deaminase, a gene involved in the pyrimidine salvage pathway, is upregulated in various #TherapyResistant cancers, including #PDAC. The gene contributes to a buildup of extracellular uridine diphosphate, which binds to the P2Y6 receptor on tumor-associated macrophages, sustaining an immunosuppressive environment. 🧪 By inhibiting cytidine deaminase in cancer cells or blocking P2Y6 in TAMs, the team demonstrated a remarkable increase in cytotoxic T cell activity, making resistant PDAC and melanoma more susceptible to anti-PD-1 therapies. These findings highlight CDA and P2Y6 as promising #NewTargets in the fight against cancer immunotherapy resistance. 💡With PDAC's grim prognosis and the doubling incidence projected by 2030, innovative approaches like this are critical. Targeting cytidine deaminase and P2Y6 could open doors to more effective #treatments for patients facing limited options, especially for those with unresectable tumors or at high risk of relapse. 📜 Congratulations to the whole team: Tommaso Scolaro, Marta Manco, Mathieu Pecqueux, Ricardo Amorim, Rosa Trotta, Heleen H. Van Acker, Matthias Van Haele, Niranjan Shirgaonkar, Stefan Naulaerts, Jan Daniluk, Fran Prenen, Chiara Varamo, Donatella Ponti, Ginevra Doglioni, Ana Margarida Ferreira Campos, Juan Fernandez Garcia, Silvia Radenkovic, Pegah Rouhi, Aleksandar Beatovic, Liwei Wang, Yu Wang, Amalia Tzoumpa, Asier Antoranz, Ara Sargsian, Mario Di Matteo, Emanuele Berardi, Jermaine Goveia, Bart Ghesquière, Tania Roskams, Stefaan Soenen, Thomas Voets, Bella Manshian, Sarah-Maria Fendt, Peter Carmeliet, Abhishek D. Garg, Ramanuj Dasgupta, Baki Topal & Massimiliano Mazzone.

⚕️A New Tool Opens New Avenues for Targeted Therapies in Colorectal Cancers ⚕️ 👩🏻🔬👨🏻🔬We are thrilled to congratulate Giorgio Corti, from the group of Sabrina Arena and Alberto Bardelli from the Università degli Studi di Torino and Candiolo Cancer Institute IRCCS on their remarkable breakthrough in colorectal cancer research! 🧬 Their latest study reveals that up to 15% of colorectal cancers harbor defects in the #homologous #recombination pathway—a phenomenon known as "BRCAness" previously associated mainly with breast and ovarian cancers. This discovery opens new avenues for targeted therapies in #colorectalcancers patients using #PARP inhibitors like olaparib. 🔬They developed an innovative #tool called HRDirect, which predicts HR deficiency from tumor samples without the need for matched normal tissue. In validation studies, HRDirect outperformed commercial assays like AmoyDx HRD and TruSight Oncology 500 HRD in accurately predicting responses to PARPi. By integrating HRDirect with ATM and RAD51C immunohistochemical analysis in a "composite #biomarker approach," they significantly enhanced the identification of HR-deficient tumors. 💉This approach offers a promising pathway for personalized treatment strategies in colorectal cancer, addressing a critical #unmetmedicalneed for patients with limited therapeutic options. ⚕Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related deaths, claiming nearly 900,000 lives annually. Despite advancements, many patients—especially those with #MicrosatelliteStable colorectal cancer —face limited treatment options and poor prognosis. This research addresses a critical unmet medical need by paving the way for personalized treatments targeting genetic vulnerabilities in colorectal cancers. 👏 Kudos to the whole research group: Giorgio Corti, Kristi Buzzo, Enrico Berrino, Martina Miotto, Maria Costanza Aquilano, Marilena Lentini, Sara Erika Bellomo, Annalisa Lorenzato, Alice Bartolini, Gianluca Mauri, Luca Lazzari, Mariangela Russo, Federica Di Nicolantonio, Salvatore Siena, Silvia Marsoni, Caterina Marchiò, Alberto Bardelli and Sabrina Arena Read below the full paper ⤵️

🧠 Targeting the brain's immune system to fight neurodegeneration in Parkinson's Disease 🧠 👏 Congratulations to Simone Bido from the group of Silvia Gregori and Broccoli Vania for leading this groundbreaking research that highlights the potential of microglia-specific IL-10 gene delivery in treating Parkinson's disease. 🧠 In the brain, IL-10 helps control the activation of microglia, the resident immune cells. Overactive microglia can cause neuroinflammation, which is implicated in the progression of diseases like Parkinson's disease. Therefore, IL-10 helps restore microglial homeostasis, potentially protecting neurons from additional damage. 📑 The study, published in Science Magazine Translational Medicine, demonstrates a promising therapeutic strategy to improve long-term outcomes for Parkinson's disease patients by slowing or halting the progression of the disease, particularly in its early stages. 🏥 The team from Ospedale San Raffaele used a unique microRNA-detargeting system, enabling localized expression of IL-10 in microglia, which in turn led to reduced dopaminergic neuron loss and enhanced the brain’s natural clearance mechanisms, offering a potential disease-modifying treatment. 🧑🦳 These findings open up new avenues for addressing unmet medical needs in Parkinson's disease by limiting systemic side effects and focusing on specific immune responses. 🚀 The ability to stimulate protective immune responses while avoiding widespread immune suppression could be a game changer in PD treatment and beyond. 🧑🔬 Kudos to the whole team: Simone Bido, Melania Nannoni, Sharon Muggeo, Diana Gambarè, Giorgia Ruffini, Edoardo Niccolò Bellini , Laura Passeri, Silvia Iaia, Mirko Luoni, Martino Provinciali, Serena Gea Giannelli, Francesca Giannese, Dejan Lazarevic, Silvia Gregori and Broccoli Vania! For more details read the paper below ⤵️

💍 Put a RING on It: New therapy targets and destroys tau tangles 💍 Congratulations to Guido Papa and Lauren Miller from the group of William A McEwan and Leo C James for their groundbreaking work on a novel approach to degrade pathogenic tau assemblies and improve motor function, which tackles a crucial unmet medical need: the treatment of tau-related neurodegenerative diseases such as #Alzheimer's and #ProgressiveSupranuclearPalsy. 🇮🇹 It is particularly exciting to note that Italian researcher Guido Papa from the MRC Laboratory of Molecular Biology (LMB) played a key role in this study, which introduces the RING-Bait technology. This innovative strategy hijacks the process of templated aggregation to recruit ubiquitination machinery, targeting harmful tau assemblies and preventing new ones from forming—all without affecting the functional protein. 🧬 RING-Bait Technology is a novel approach that recruits ubiquitin ligase machinery into pathogenic tau aggregates, triggering their degradation. The technology selectively degrades pre-existing aggregates and prevents new aggregates from forming, without targeting soluble tau proteins, ensuring that normal cellular functions are unaffected. 🧠 Remarkably, the study demonstrated that RING-Bait technology effectively reduces tau pathology and improves motor function in vivo, offering hope for potential future applications in treating Alzheimer’s disease and PSP. 📄 The RING-Bait degraders work against tau aggregates derived from human brain samples, specifically targeting seeded tau aggregation, a major challenge in neurodegenerative diseases. 🏥 These insights not only advance our understanding of tau pathology but also provide a promising therapeutic avenue for degrading intracellular protein aggregates. This method may pave the way for future gene therapy treatments for neurodegenerative diseases characterized by the accumulation of misfolded proteins. 👏 Congratulations to the entire team behind this significant achievement: Lauren V.C. Miller, Guido Papa, Marina Vaysburd, Shi Cheng, Paul W. Sweeney, Annabel Smith, Catarina Franco, Taxiarchis Katsinelos, Melissa Huang, Sophie A.I. Sanford, Jonathan Benn, Jasmine Farnsworth, Katie Higginson, Holly Joyner, William A McEwan, Leo C. James Below the full paper ⤵ #neuroscience #tauopathy #research #biotech #neurodegeneration #scientificinnovation #RINGBaitTechnology

🌟 Pathway Vulnerabilities Uncovered for Enhanced Therapeutic Strategies 🌟 Congratulations to Johanna Zerbib, Marica Rosaria Ippolito from the group of Stefano Santaguida, PhD and Uri Ben-David for their groundbreaking work recently published in Nature Portfolio Communications on aneuploidy and cancer. 🔬 This study reveals that human aneuploid cells, a hallmark of cancer, depend on the RAF/MEK/ERK pathway to cope with increased DNA damage. 🧬 By inducing chromosome mis-segregation in non-transformed cells, the research team uncovered several critical insights: Aneuploid cells activate the DNA damage response and are more resistant to additional damage. These cells show elevated RAF/MEK/ERK pathway activity, making them particularly sensitive to inhibitors targeting this pathway, notably CRAF. 🧪Importantly, inhibiting the RAF/MEK/ERK pathway sensitizes aneuploid cells to DNA damage-inducing chemotherapies and PARP inhibitors, with clinical relevance in improving cancer treatment strategies. 🏥 This research has immense implications for addressing unmet medical needs in cancer treatment, particularly in targeting the vulnerabilities of highly-aneuploid tumors. It paves the way for improved therapies that can potentially overcome resistance to existing drugs like olaparib. 👏 Huge congratulations to the entire team for their impactful contribution to the field Johanna Zerbib, Marica Rosaria Ippolito, Yonatan Eliezer, Giuseppina De Feudis, Eli Reuveni, Anouk Savir Kadmon, Sara Martin, Sonia Viganò, Gil Leor, James Berstler, Julia Muenzner, Michael Muelleder, Emma Campagnolo, Eldad Shulman, Tiangen CHANG, Carmela Rubolino, Kathrin Laue, Yael Cohen Sharir, Simone Scorzoni, Silvia Taglietti, Alice Ratti, Chani Stossel, Talia Golan, Francesco Nicassio, Eytan Ruppin, Markus Ralser, Francisca Vazquez, Uri Ben-David and Stefano Santaguida, PhD. Thanks to all the italian supporters: Fondazione AIRC per la Ricerca sul Cancro ETS IEO Istituto Europeo di Oncologia Università degli Studi di Milano SEMM - Scuola Europea di Medicina Molecolare Below the full paper ⤵

💡 Revolutionary Mitochondrial Transfer Boosts T Cell Fitness and Antitumor Efficacy💡 👏 Congratulations to Jeremy Baldwin from the group of Luca Gattinoni and Shiladitya Sengupta for their groundbreaking work on intercellular mitochondrial transfer, enhancing T cell metabolic fitness and antitumor efficacy. 🔍 This study introduces a novel platform that leverages bone marrow stromal cells to transfer healthy #mitochondria to CD8+ T cells, overcoming T cell exhaustion—one of the biggest barriers in #immunotherapy for #cancer. By enhancing mitochondrial respiration and resistance to exhaustion, the team showed that mitochondria-boosted T cells could expand more robustly, infiltrate tumors more efficiently, and deliver superior antitumor responses, ultimately prolonging survival in preclinical models. 💊 The findings are highly relevant to the unmet medical need in cancer immunotherapy, particularly for solid tumors. Current therapies often face challenges with T cell #exhaustion due to a hostile tumor #microenvironment. The introduction of this mitochondrial transfer technology represents a significant advancement in organelle medicine, opening new pathways for more effective cell therapies. 🥼 Luca Gattinoni, with his extensive background in immunotherapy and cellular engineering, has been instrumental in pushing the boundaries of adoptive T cell therapies. 🏛️ This work highlights the importance of multidisciplinary and multinational collaborations, demonstrating how joint efforts across institutions like the The National Institutes of Health, LIT - Leibniz Institute for Immunotherapy, Harvard-MIT Health Sciences and Technology (HST) and institutions like the IRCCS Ospedale San Raffaele, showcasing the critical role of global partnerships in pushing the limits of innovation in cancer treatment. 👏 Kudos to the entire research team: Jeremy G. Baldwin, Christoph Heuser-Loy, Tanmoy Saha, Roland C. Schelker, Dragana Slavkovic Lukic, Nicholas Strieder, Inmaculada Hernandez-Lopez, Nisha Rana , Markus Barden, Fabio Mastrogiovanni, Azucena Martín-Santos, Andrea Raimondi, Philip "Zach" Brohawn, Brandon W. Higgs, Claudia G., Veena Kapoor, William G. Telford, Sanjivan G., Maria Xydia, Philipp Beckhove, Sina Frischholz, Kilian Schober, Zacharias Kontarakis, Jacob E. Corn, Matteo Iannacone, Donato Inverso, Michael Rehli, Jessica Fioravanti, Shiladitya Sengupta, and Luca Gattinoni. Read below the full paper ⤵

🚨 Innovative Immunotherapy for HER2-Amplified Colorectal Cancer 🚨 👏 Huge congratulations to Marco Cortese, Enzo Medico and Dario Sangiolo from Candiolo Cancer Institute IRCCS, Università degli Studi di Torino for their outstanding work on the recent publication in Molecular Therapy! 📑 This paper presents a novel approach to treating HER2-amplified colorectal cancer, a type of cancer that affects approximately 5% of CRC patients and is often resistant to traditional HER2/EGFR-targeted therapies. The research team has developed an innovative combinatorial immunotherapy that uses an engineered natural killer cell line (NK-92) equipped with a HER2-synNotch receptor and a CAR targeting carcinoembryonic antigen. This unique design ensures that the CAR is expressed only when both HER2 amplification and CEA expression are present, significantly improving the precision and safety of the therapy. Here are the key findings: 👨🔬 The NK-92 cells express the CAR only when both HER2 amplification and CEA expression are detected, improving tumor specificity and significantly reducing off-target toxicity. 🏥 The HER2-synNotch/CEA-CAR-NK system demonstrated strong anti-tumor effects both in vitro and in vivo specifically against HER2-amplified/CEA+ colorectal cancer models. 🌿 This method avoids the severe side effects seen in previous CAR-T therapies, ensuring that healthy cells with physiological HER2 levels remain unharmed. 🔬 The HER2-synNotch/CEA-CAR-NK system is scalable and safe, providing an accessible treatment option for HER2amp CRC patients who are resistant to existing HER2/EGFR treatments. ⚕ This research opens up exciting new possibilities for more effective and safer treatments for HER2-amplified colorectal cancer! 🧬 👏 Congratulations to the whole team: Marco Cortese, Erica Torchiaro, Alice D'Andrea, Consalvo Petti, Federica Invrea, Letizia Franco, Chiara Donini, PhD, Valeria Leuci, Simonetta Maria Leto, Valentina Vurchio, Francesca Cottino, Claudio Isella, Sabrina Arena, Elisa Vigna, Andrea Bertotti, Livio Trusolino, Dario Sangiolo, Enzo Medico. #CancerResearch #HER2Amplification #Immunotherapy #CARNKCells #ColorectalCancer Read the full paper below ⤵

🧬 Exciting Breakthrough in Gene Therapy! 🧬 📑 Huge congratulations to Federica Esposito, from Alberto Auricchio and Toni Cathomen from Fondazione Telethon Tigem for their outstanding work on the recent publication in Cell Reports Medicine! 🧬 Gene therapy has long held promise for addressing inherited liver diseases such as #Mucopolysaccharidosis VI and #Hemophilia A. These are devastating genetic disorders that lead to enzyme deficiencies or impaired blood clotting, severely affecting quality of life. While traditional treatments are available, they often require frequent administration, are not curative, and may have significant side effects. For instance, Mucopolysaccharidosis VI causes an accumulation of glycosaminoglycans, leading to multi-organ damage, while Hemophilia A results in bleeding episodes due to a lack of clotting factor VIII. 💊 This groundbreaking research highlights the development of AAV-HITI, a liver-directed, adeno-associated viral vector-mediated homology-independent targeted integration method using CRISPR-Cas9. By targeting the #liver, this strategy allows for stable, long-term production of therapeutic proteins, which could significantly improve treatment for such genetic disorders. Here are the key findings: 🔬 AAV-HITI provides stable and therapeutic protein levels in the liver from both newborn and adult mouse models, showing promise for long-term treatment. Effectiveness in genetic diseases: AAV-HITI successfully targets the liver and achieves therapeutic benefits in mouse models of inherited diseases like MPS VI and Hemophilia A. 🌿 With no detectable off-target effects or chromosomal rearrangements and safety proven for up to a year, this technique shows minimal risks. Broad therapeutic potential: Effective at doses safe for humans, this could be a game changer for patients needing liver-targeted gene therapies, addressing unmet needs in early-onset metabolic diseases. ⚕ This research opens the door to innovative treatments for inborn genetic disorders! 🧬 Congrats to the whole team: Federica Esposito, Fabio Dell´Aquila, Manuel Rhiel, Stefano Auricchio, Kay Ole Chmielewski, Geoffroy Andrieux, Rita Ferla, Paula Sureda Horrach, Arjun Padmanabhan, Roberto Di Cunto, Simone Notaro, Manel Llado Santeularia, Melanie Boerries, Margherita Dell’Anno, Edoardo Nusco, Agnese Padula, Sofia Nutarelli, Tatjana I. Cornu, Nicolina Cristina Sorrentino, Pasquale Piccolo, Ivana Trapani, Toni Cathomen, Alberto Auricchio. Full paper below ⤵