Abstract 5545: Dynamic Precision™: a scalable tech-bio platform to identify immune-mediated resistance through dynamic monitoring
Authors: Ronan O'Hagan, Lynda Chin
Journal: Cancer Research (2025)

Abstract Background: Understanding immune-mediated resistance requires recognizing the immune system as a complex adaptive system and studying its dynamic responses to drugs in diverse patient populations. Current approaches are hindered by (1) reliance on static, pre-treatment tumor analyses or preclinical models, and (2) sampling bias, as 80% of cancer patients are treated in community settings without enrollment in translational research. We hypothesized that combining dynamic analysis of immune response on treatment with broader patient representation would reveal previously unrecognized resistance mechanisms. Methods: We developed a tech-bio platform to overcome these limitations. First, applying complex system insights, we pioneered Dynamic Precision™, a AI/ML-based approach to identify emerging resistance targets and blood-based biomarkers from longitudinal patient data. Second, we developed ApricityCare, a HIPAA-compliant virtual care service, to engage diverse populations outside academic institutions in research under the SMART (Serial Molecular and Clinical Annotation of Responses to Therapies) protocol. SMART is IRB-approved for serial liquid biopsy collection, incorporating ApricityCare to enable research-grade data collection. ApricityCare offers 24/7 symptom monitoring and virtual management by nurses augmented with a clinical intelligence co-pilot, ensuring standardized side effect management, documentation, and automated data capture. Coupled with mobile phlebotomy, SMART reduces participation burdens for providers and patients. Results: We analyzed longitudinal clinical and serial plasma proteomic data from melanoma patients on standard-of-care ICI therapy. Dynamic Precision™ identified early on-treatment signatures predictive of treatment failure and uncovered dynamically regulated immune proteins as potential therapeutic targets. Triangulation with clinical insights revealed druggable immune regulators with validated resistance mechanisms to T-cell checkpoint inhibitors. In parallel, ApricityCare demonstrated its ability to provide proactive symptom monitoring and side effect management while capturing high-quality clinical data without increasing workload for in-clinic care team. Leveraging mobile phlebotomy, SMART has been piloted successfully in multiple states. Conclusions: We demonstrate here a dynamic approach to identifying immune-mediated resistance mechanisms, with a blood-based biomarker strategy for longitudinal monitoring to detect the molecular signals of resistance months before clinical progression of disease. With ApricityCare-enabled SMART protocol, we have also a scalable platform to bridge the representation gaps, generating more inclusive datasets to elucidate a more diverse range of drug resistance mechanisms. Proof-of-concept data will be presented. Citation Format: Ronan O'Hagan, Lynda Chin. Dynamic Precision™: a scalable tech-bio platform to identify immune-mediated resistance through dynamic monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5545.