Engineered human sialidase as a novel cancer therapeutic targeting immune-suppressive sialoglycans in tumors

Engineered human sialidase as a novel cancer therapeutic targeting immune-suppressive sialoglycans in tumors | 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 Engineered human sialidase as a novel cancer therapeutic targeting immune-suppressive sialoglycans in tumors Li Peng, Lizhi Cao, Sandip Shelke, Autumn Turner, Jenny Che, Zakir Siddiquee, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6667049/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 Immune checkpoint blockade has revolutionized cancer therapy, but resistance in many patients highlights the need for new approaches. Sialoglycans, recognized as novel immune checkpoints, can be therapeutically targeted to enhance anti-tumor immunity. Tumor-targeted antibody-bacterial sialidase conjugates have shown antitumor activity preclinically, but immunogenicity risks limit their clinical use. To address this, we engineered a human sialidase, E-602 (eNeu2), with improved stability, developability, and a production titer of ~3 g/L, a major advance over the near-zero yield of the wild-type enzyme. E-602’s higher Km compared to bacterial sialidases enables selective desialylation of tumor and immune cells with abundant surface sialoglycans, while sparing healthy cells, achieving a favorable safety profile without a tumor-targeting moiety. E-602 alleviated sialoglycan-mediated immunosuppression and enhanced immune effector functions in human immune assays. In syngeneic mouse models, it showed single-agent anti-tumor activity and was well tolerated at doses up to 100 mg/kg in non-human primates, supporting its clinical potential. Biological sciences/Drug discovery/Biologics Biological sciences/Cancer/Cancer microenvironment Health sciences/Molecular medicine Full Text Additional Declarations All animal studies were approved by the Institutional Animal Care and Use Committees (IACUCs) at the respective research facilities, including Altasciences, Charles River Laboratories, Champions Oncology, and Crown Bioscience, and were conducted in accordance with all applicable guidelines and regulations. Yes there is potential Competing Interest. Authors are employees of Palleon. Supplementary Files April2025SupplementalFigures.pdf Supplemental Figures 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6667049","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":470987678,"identity":"607e1d34-3632-44a3-af63-72bab4f75156","order_by":0,"name":"Li 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