Evaluating xenograft mouse models for preclinical assessment of adoptive T cell transfer

Evaluating xenograft mouse models for preclinical assessment of adoptive T cell transfer | 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 Evaluating xenograft mouse models for preclinical assessment of adoptive T cell transfer Siri Tvingsholm, Marcus Frej, Nithiyashri Jayashankar, Kristoffer Johansen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6528016/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 Humanized mouse models are crucial for preclinical testing of adoptive cell transfer (ACT) strategies in cancer immunotherapy. A key challenge is identifying models that enable efficient human T cell engraftment while minimizing graft-versus-host disease (GVHD), which hinders long-term assessment of T cell functionality. The immunodeficient NOD/SCID/IL-2Rγnull (NOG) mouse strain with transgenic expression of human interleukin-2 (hIL-2-NOG) has recently been proposed as a promising model for ACT, since it supports engraftment and promotes T cell survival in vivo. However, in the present study we found that hIL-2-NOG mice adoptively transferred with ex vivo-expanded human T cells, rapidly developed GVHD in a dose-dependent manner. Comparing adoptive transfer of fresh and cryopreserved human T cells in hIL-2-NOG, parental NOG and NOG mice with a beta-2-microglobulin deletion (B2m-NOG) that delays GVHD onset, demonstrated that engraftment and GVHD induction were limited to hIL-2-NOG mice, while NOG and B2m-NOG showed poor donor T cell engraftment. Cryopreservation delayed GVHD onset in hIL-2-NOG mice, likely due to reduced T cell viability and functionality. Additionally, introducing a tumor expressing the T cell target antigen enhanced T cell engraftment in NOG mice, indicating that antigen recognition can improve survival and persistence of transferred T cells. These findings suggest that several factors influence the capacity of human T cells to engraft following adoptive transfer in xenogeneic mouse models, including the genetic background of recipient mice, and the quantity and functionality of transferred T cells. Thus, these factors should be considered when choosing a preclinical mouse model for evaluation of ACT strategies. Health sciences/Oncology/Cancer/Cancer therapy/Cancer immunotherapy Health sciences/Oncology/Cancer/Cancer models Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations (Not answered) Supplementary Files Suppl.figuresCMI.pdf Supplementary Figures and Tables 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-6528016","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":450056990,"identity":"4acf88e4-847c-45e3-9899-20ab558b4003","order_by":0,"name":"Siri 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A key challenge is identifying models that enable efficient human T cell engraftment while minimizing graft-versus-host disease (GVHD), which hinders long-term assessment of T cell functionality. The immunodeficient NOD/SCID/IL-2Rγnull (NOG) mouse strain with transgenic expression of human interleukin-2 (hIL-2-NOG) has recently been proposed as a promising model for ACT, since it supports engraftment and promotes T cell survival in vivo. However, in the present study we found that hIL-2-NOG mice adoptively transferred with ex vivo-expanded human T cells, rapidly developed GVHD in a dose-dependent manner. Comparing adoptive transfer of fresh and cryopreserved human T cells in hIL-2-NOG, parental NOG and NOG mice with a beta-2-microglobulin deletion (B2m-NOG) that delays GVHD onset, demonstrated that engraftment and GVHD induction were limited to hIL-2-NOG mice, while NOG and B2m-NOG showed poor donor T cell engraftment. 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