Automated plasma EV-PDL1 analysis for cancer immunotherapy

ABSTRACT 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 at a considerable cost. The most validated and FDA-approved biomarker to guide patient selection is through immunohistochemical (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 which is sometimes difficult to perform; ii) the site and timing of tissue acquisition and staining protocols can influence the accuracy of TPS; iii) IHC takes days to process, delaying treatment; iv) many TPS-positive patients do not respond 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 assay based 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 expression from primary and metastatic lesions can be a more comprehensive marker. We propose two specific aims. Aim 1. 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 assay and integrated scores can be utilized in clinical trials testing anti-PD1/PD-L1 mono- or combination therapies. It can provide a faster and more reliable solution for evaluating treatment response, and help accelerate regulatory decision-making.