Buddy-CAR NK cells: IL-7/IL-7Rα cytokine circuit drives self-activation and boosts T cell immunity

Buddy-CAR NK cells: IL-7/IL-7Rα cytokine circuit drives self-activation and boosts T cell immunity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Buddy-CAR NK cells: IL-7/IL-7Rα cytokine circuit drives self-activation and boosts T cell immunity Rizwan Romee, Andreia Maia, Mubin Tarannum, Sara Piccinelli, Eric de Sousa, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7762552/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Adoptive cell therapy has revolutionized the treatment of hematologic malignancies, yet efficacy in solid tumors remains limited by poor persistence, immunosuppressive tumor microenvironment (TME), and toxicity concerns. Natural killer (NK) cells provide an attractive alternative to T cells, offering potent cytotoxicity with reduced risk of cytokine release syndrome, neurotoxicity, and graft versus host disease. However, NK cell therapies are hindered by a short lifespan with limited in vivo persistence. Here, we establish Buddy-CAR, a first-in-class NK cell platform that integrates the IL-7/IL-7Rα cytokine circuit to create self-sustaining NK cells that also amplify T-cell immunity. This novel dual-function design reprograms NK cells into living immune hubs that maintain metabolic fitness and persistence while enhancing CAR-T expansion, effector function, and resistance to exhaustion. Mechanistically, Buddy-CAR engaged STAT1/STAT5 signaling axis and synergized with STING activation, driving heightened interferon responses. This self-sustaining and immunomodulatory design improved tumor control across models of pancreatic cancer, acute myeloid leukemia, and mixed xenografts. These findings establish Buddy-CAR NK cells as a versatile platform that integrates NK cell intrinsic fitness with extrinsic T cell support, offering a promising strategy for overcoming immune suppression in solid and hematologic malignancies. Biological sciences/Immunology/Immunotherapy Biological sciences/Immunology Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7762552","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":526012115,"identity":"26dc47aa-3c4c-4385-b1ee-be1929c248ce","order_by":0,"name":"Rizwan 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