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.

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

Amato L.;Tavoletta I.;De Rosa C.;Arcadio F.;Capaldo S.;Tuccillo C.;Esposito C.;di Guida G.;Iommelli F.;De Rosa V.;Reginelli A.;Cappabianca S.;Morgillo F.;Ciardiello F.;Nardone V.;Cennamo N.;Della Corte C. M.;
2026

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/595107
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