Proof-of-concept study of clinical use of blood-based MAVS biosensor in predicting immunotherapy response in SCLC patients

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with poor prognosis and limited benefit from immune checkpoint inhibitors (ICIs). Biomarker-driven patient stratification has been hindered by small biopsy samples, high tumor heterogeneity, and the limited predictive value of PD-L1 and tumor mutation burden. Mitochondrial antiviral-signaling protein (MAVS) has emerged as a potential immune activation marker, particularly in patients receiving DNA-damaging therapies. We report a proof-of-concept clinical study evaluating a surface plasmon resonance-plastic optical fiber (SPR‑POF) biosensor functionalized with anti-MAVS antibodies to detect the protein in serum from SCLC patients undergoing chemo-immunotherapy, with or without radiotherapy. The biosensor achieved a limit of detection of 0.13 nM in human diluted serum and demonstrated high selectivity against common serum proteins. In a cohort stratified as best responders (disease control >6 months) and non-responders (progressive disease as best response), MAVS levels measured in responders were on average tenfold higher than in non-responders, consistent with previous preclinical PBMC and western blot data. The SPR‑POF platform demonstrated portability, cost-effectiveness (estimated 5 USD/unit), and operational simplicity, highlighting its potential for point-of-care testing (POCT) applications. Although limited by small patient numbers, these findings support MAVS as a promising predictive biomarker in SCLC, warranting validation in larger prospective studies.