IMMUNOPHENOTYPING CORE The promising clinical efficacy of immune checkpoint inhibitors for a significant number of cancer types has been dogged by inconsistent biomarkers, incomplete toxicity profiles, and non-validated correlative studies that have not fostered next generation of clinical trials based on clear mechanistic studies to address immune resistance mechanisms. For breast cancer, immunotherapy-based trials have expanded, but predictive biomarkers remain poorly defined. Thus, there remains an unmet need for a comprehensive characterization of clinically relevant biomarkers for breast cancer immunotherapy-based trials. In this SPORE proposal, we have introduced two immunotherapy-based trials (Projects 2 and 4) and another trial that can be interrogated for future combination with immune checkpoint inhibitors (Project 3). Given the critical need for a concerted and coordinated analysis platform for immune monitoring and assessment, we propose to establish an Immunophenotyping Core (IPC). We have both well established and state-of-the-art immunological assay platforms that can analyze biospecimens collected from ongoing clinical trials to enable rational translational efforts of combinatorial immunotherapy and to provide comprehensive clinical toxicity profiling on patients undergoing these immunotherapy trials. IPC proposes to provide validated analytic platforms to include CyTOF, robust single cell TCR sequencing, multispectral immunofluorescence, flow cytometry, whole exome and RNA sequencing. Vanderbilt has recently led the efforts to comprehensively characterize the clinical toxicity profile of immune checkpoint inhibitors, and we will synchronize these efforts to standardize immune toxicity profiling on patients enrolled in breast cancer immunotherapy clinical trials. IPC will also incorporate translational technologies from Vanderbilt University Institute of Imaging Science (VUIIS) to promote immuno-imaging methods to advance non- invasive tumor correlative studies in conjunction with the proposed clinical trials. IPC will help to establish clinically relevant biomarkers and immune-toxicity profiles that can precisely define the therapeutic window for breast cancer immunotherapeutic platforms and potentially define the next generation of breast cancer immunotherapy-based studies.
IMMUNOPHENOTYPING CORE In concordance with the mission statement of NIH, this proposal seeks to obtain knowledge of cancer therapy and cancer management by generating clinically pertinent biomarkers derived from samples from the Vanderbilt-Ingram Cancer Center SPORE in Breast Cancer clinical trials. The Immunophenotyping Core will characterize these biospecimens for the purpose of enhancing the health of cancer patients.
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