Abstract 2099: Leveraging spatial transcriptomics and proteomics to assess the Immune response and DNA damage in high grade serous ovarian cancer (HGSOC) treated with neoadjuvant chemotherapy

Abstract Ovarian cancer is the sixth leading cause of cancer-related deaths among women in the United States. Many women (>80%) with OC are diagnosed at an advanced stage and a 5-year survival rate of less than 30%. Newer therapies, such as antibody-drug conjugates (ADCs), have revolutionized the treatment landscape for solid tumors, including ovarian cancer. While platinum-based chemotherapy stays the stalwart in systemic therapy for OC treatment, most of these patients experience recurrence (>50%) despite receiving standard of care therapy. Hence, significant efforts are made to target candidates for a personalized approach to therapy. 9 eligible patients with biopsy confirmed, newly diagnosed, advanced-stage serous EOC deemed appropriate for NACT seen at the University of Alabama at Birmingham Gynecologic Oncology clinic were recruited. EMR was reviewed and demographic, survival, surgery, and tumor response data were collected. Target receptor expression pre and post ADC treatment was also evaluated using IHC staining of the target protein. Actively, we are using spatial transcriptomics and proteomics to assess DNA damage and tumor immune microenvironment (TIME) pre and post NACT. Repair assisted damage detection (RADD) assay, The Lunaphore COMET and Nanostring GeoMx platform will all be utilized to perform this analysis. The RADD assay gives a DNA damage score that will be compared pre- and post-treatment. The Lunaphore COMET antibody staining panel will include antibodies against the surface and intracellular proteins pan-cytokeratin, CD3, CD4, CD5, CD8, CD20, CD25, CD31, CD68, DAPI, Granz B, FOXP3, CXCR3, CXCR5, CCR6, CTLA4, PD-1, PDL1, TIM3, and pan-cytokeratin, allowing us to evaluate changes in subpopulations within the tumor immune microenvironment in response to ADCs in combination with platinum therapy. NanoString GeoMX platform will use targeted transcriptomic sequencing to further evaluate PanCK+ tumor cells, CD20+ B cells, and CD8+ T cells, or subpopulations identified from COMET results. Results Median age of this cohort was 68.5 (52-81), most patients were white (n=7), all patients had stage III or IV disease (n=9). Based on RECIST 1.1 criteria, median change in tumor burden from baseline was -19.31% (+9.81% to -85.64%), showing the impact of NACT. The secondary outcomes of this study are to identify predictive biomarkers as potential therapeutic targets through analysis proteomics and transcriptomics. ADCs have demonstrated potential to monitor change in tumor burden, thereby validating the efficacy of targeted therapy based on protein or receptor expression in OC. Utilizing technologies such as COMET and Nano-string, our results will help us understand the intricacies of NACT therapy in the context of ADCs and contribute to pave the way for a more tailored therapeutic approach. Citation Format: Dhruva Dave, Natalie R. Gassman, Emily O'brein, Fibiana Oladipo, Rebecca Arend. Leveraging spatial transcriptomics and proteomics to assess the Immune response and DNA damage in high grade serous ovarian cancer (HGSOC) treated with neoadjuvant chemotherapy [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 2099.