Nano-ImmunoEra · NANOTECHNOLOGY-ENABLED DETECTION OF CLINICALLY RELEVANT ANTIBODIES FOR EARLY CANCER DIAGNOSIS AND IMMUNOTHERAPY MONITORING

NANOTECHNOLOGY-ENABLED DETECTION OF CLINICALLY RELEVANT ANTIBODIES FOR EARLY CANCER DIAGNOSIS AND IMMUNOTHERAPY MONITORING

Current methods for the quantitative detection of clinically-relevant antibodies mostly rely on enzyme linked immunosorbent assays (ELISAs), Western blots, and polarization assays, which are multistep, wash- and reagent-intensive processes that require sophisticated instrumentations that limit their applicability in point-of-care (POC) diagnostics and high-throughput assays. Point-of-care disposable tests instead allow more frequent diagnostic screening, especially in low in-come countries, and shortens the delay between sample acquisition, diagnosis and therapeutic decisions in clinical settings. The goal of Nano-ImmunoEra network is to transfer the knowledge from “the bench” to real clinical practices for developing the next generation of sensing platforms able to detect multiple tumor-associated antibodies in order to improve early cancer diagnosis, effective prognosis and immunotherapy monitoring. We will demonstrate the feasibility and validate adaptability of the Nano-ImmunoEra diagnostic tools for the rapid, sensitive and multiplex detection of serological tumor-associated autoantibody and this would potentially have a significant impact on early diagnosis of cancer-affected patients at all stages. Nano-ImmunoEra platform will use as transduction mechanism, electrochemiluminescence (ECL) that -because it offers high sensitivities – is already the leading signal-transduction technique in many important clinical analyses. In ECL, the light emission is triggered by an electrochemical reaction requiring voltages lower than common batteries, without the need of lamps or lasers; for all these reasons it can allow the construction of portable, low-cost devices. key objectives: - Identification and optimization of selective recognition elements for clinically-relevant antibody detection; KPI1: High binding affinity (KD < 10-12 M) - Preparation of novel nanostructured electrode material and ECL signal transduction; KPI2 costs < 1 euro/electrode. - Understanding and optimizing of the parameters controlling the electrochemiluminescence transduction method; KPI3: “per molecule” analytical signal intensity > 100 times that of Ru(bpy)32+/TPA; Noise < 10 times less than the Ru(bpy)32+ system. - Combining of programmable antibody-responsive nucleic acid devices and CRISPR-based amplification; KPI4: ~ 2 orders of magnitude higher sensitivity compared to direct affinity-based detection - Real‐time monitoring of therapeutic antibodies in whole blood KPI5: Trastuzumab, Cetuximab LOQ = 10 µg ml-1; dynamic range between 5 and 180 µg ml-1 - Development of a portable ECL platform for rapid, easy to use TAA detection KPI6: anti-p53 autoantibody, anti-MUC1 autoantibody LOQ < 5 ng ml-1 The final step will be the evaluation with model samples and the comparison with the state-of-the-art biosensing technologies.

Data: CORDIS, © European Union