Mathematical Modeling Insights into Improving CAR T cell Therapy for Solid Tumors: Antigen Heterogeneity and Bystander Effects

Mathematical Modeling Insights into Improving CAR T cell Therapy for Solid Tumors: Antigen Heterogeneity and Bystander Effects | 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 Mathematical Modeling Insights into Improving CAR T cell Therapy for Solid Tumors: Antigen Heterogeneity and Bystander Effects Rockford Sison, Erdi Kara, Reginald McGee II, tracy jackson, Chartese Jones This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3789062/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Sep, 2024 Read the published version in npj Systems Biology and Applications → Version 1 posted 10 You are reading this latest preprint version Abstract As an adoptive cellular therapy, Chimeric Antigen Receptor T-cell (CAR T-cell) therapy has shown remarkable success in hematological malignancies but only limited efficacy against solid tumors. Compared with blood cancers, solid tumors present a series of challenges that ultimately combine to neutralize the function of CAR T-cells. These challenges include, but are not limited to, antigen heterogeneity - variability in the expression of the antigen on tumor cells, as well as trafficking and infiltration into the solid tumor tissue. A critical question for solving the heterogeneity problem is whether CAR T therapy induces bystander effects, such as antigen spreading. Antigen spreading occurs when CAR T-cells activate other endogenous antitumor CD8 T cells against antigens that were not originally targeted. In this work, we develop a mathematical model of CAR T-cell therapy for solid tumors that considers both antigen heterogeneity and bystander effects. Our model is based on in vivo treatment data that includes a mixture of target antigen-positive and target antigen-negative tumor cells. We use our model to simulate large cohorts of virtual patients to better understand the relationship involving bystander killing. We also investigate several strategies for enhancing bystander effects, thus increasing CAR T-cell therapy's overall efficacy for solid tumors. CAR T-cell therapy bystander effect solid tumor mathematical modelling virtual patient Full Text Additional Declarations Supplementary Material is not available with this version Cite Share Download PDF Status: Published Journal Publication published 28 Sep, 2024 Read the published version in npj Systems Biology and Applications → Version 1 posted Editorial decision: revise 02 Feb, 2024 Review # 2 received at journal 31 Jan, 2024 Review # 3 received at journal 26 Jan, 2024 Reviewer # 3 agreed at journal 10 Jan, 2024 Reviewer # 2 agreed at journal 09 Jan, 2024 Reviewer # 1 agreed at journal 05 Jan, 2024 Reviewers invited by journal 05 Jan, 2024 Submission checks completed at journal 22 Dec, 2023 First submitted to journal 21 Dec, 2023 Editor assigned by journal 21 Dec, 2023 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. 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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-3789062","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":265439391,"identity":"67b0ed83-07b9-48ed-bb58-dc2c4d114843","order_by":0,"name":"Rockford 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