Challenges. There are over 4000 clinical trials testing anti-PD1/PD-L1 immune checkpoint inhibitors (ICI), either alone or in combination with other therapies. While many patients benefit, the vast amount do not, all ata considerable cost. The most validated and FDA-approved biomarker to guide patient selection is throug himmunohistochemical (IHC) staining and scoring of tissue biopsies for PD-L1 (e.g. Tumor Proportion Score,TPS). Unfortunately, TPS is an imperfect biomarker: i) it requires surgical or image guided tissue biopsy whichis sometimes difficult to perform; ii) the site and timing of tissue acquisition and staining protocols can influencethe accuracy of TPS; iii) IHC takes days to process, delaying treatment; iv) many TPS-positive patients do notrespond to ICI treatment; and v) TPS can change during chemo, targeted and ICI therapies.Phase I goals. Accure Health proposes to explore an alternative approach: circulating PD-L1 biomarker assaybased on Technology-integrated magneto-electronic sensing (TiMES) of extracellular vesicles (EVs).Supported by promising clinical data, we hypothesize that circulating EV analysis integrating PD-L1 expressionfrom primary and metastatic lesions can be a more comprehensive marker. We propose two specific aims. Aim1. Develop an automated TiMES assay to analyze pan EV-PDL1 and cell type-specific EV-PDL1. Aim 2.Establish TiMES EV-PDL1 scores and correlate with TPS. We envision the automated TiMES EV-PDL1 assayand integrated scores can be utilized in clinical trials testing anti-PD1/PD-L1 mono- or combination therapies. Itcan provide a faster and more reliable solution for evaluating treatment response, and help accelerateregulatory decision-making.
Public Health Relevance Statement: PROJECT NARRATIVE
We will develop an automated, plasma-based TiMES EV-PDL1 assay and digital scoring system for lung
cancer immunotherapy. We envision that a comprehensive analysis of PD-L1 biomarkers can help predict and
evaluate treatment response, and accelerate therapeutic development.
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