volume | PIER Journals

2026-10-30

A Magnetic Bead-Amplified SPR/SERS Dual-Modality Assay for EV-Associated TGF-β1 as a Companion Diagnostic for CAR-T Therapy

Sailing He,

Prof. Sailing He

Department of Electromagnetic Theory

Royal Institute of Technology

Sweden

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Faten Bashar Kamal Eddin,

Dr. Faten Bashar Kamal Eddin

College of Optical Science and Engineering, National Engineering Research Center for Optical Instruments

Zhejiang University

China

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Abdur Rahim,

Dr. Abdur Rahim

College of Optical Science and Engineering, National Engineering Research Center for Optical Instruments

Zhejiang University

China

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Wen Lei,

Dr. Wen Lei

Department of Hematology

The Second Affiliated Hospital, Zhejiang University School of Medicine

China

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Qunyi Guo,

Dr. Qunyi Guo

Department of Hematology

Taizhou Hospital of Zhejiang Province 150# Ximen Road of Linhai City

China

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Kaixin Zheng,

Mr. Kaixin Zheng

College of Optical Science and Engineering, National Engineering Research Center for Optical Instruments

Zhejiang University

China

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Raheel Ahmed Janjua,

Dr. Raheel Ahmed Janjua

Zhejiang University

China

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Wenda Luo

Dr. Wenda Luo

Sensing and Non-invasive Rapid Testing, Taizhou Hospital

Zhejiang University

China

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Progress In Electromagnetics Research Letters, Vol. 132, 43-53, 2026

DOI:10.2528/PIERL26070501 | Google Scholar

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in hematologic malignancies, yet its efficacy in solid tumors remains limited by the immunosuppressive tumor microenvironment. The recent clinical breakthrough of GPC3-specific dnTGFβRII-armored CAR-T (C-CAR031) has demonstrated encouraging responses, but a substantial fraction of patients still fails to achieve durable remission. A key resistance mechanism is the overwhelming burden of TGF-β1 in the tumor microenvironment, which may overwhelm the dnTGFβRII ``armor'' and lead to CAR-T exhaustion. Here, we report a magnetic bead-amplified phase-interrogated surface plasmon resonance (SPR) biosensor for the quantitative detection of TGF-β1 on tumor-derived extracellular vesicles (TEVs) in patient plasma. The platform combines anti-TGF-β1 antibody-conjugated magnetic beads for EV enrichment with a ZnSe/GO SPR chip functionalized with anti-TGF-β1 for real-time, label-free detection. The assay achieved a limit of detection (LOD) of 0.051 pg/mL with a linear range spanning 10^-1-10⁵ pg/mL (R² = 0.9894). In vitro, CAR-T + Raji co-culture significantly increased TGF-β1⁺ EVs compared with all control groups, peaking at 24 h. Orthogonal surface-enhanced Raman scattering (SERS) validation at 72 h independently confirmed this trend, exhibiting characteristic R6G reporter peaks at ~1367 cm^-1 and ~1520 cm^-1, and strictly following the hierarchy of CAR-T + Raji > Raji > CAR-T > CT + Raji > Healthy controls. Clinically, four CAR-T patients showed marked elevations in plasma EV-associated TGF-β1 (7.2-21.3 fold over baseline), with peak concentrations of 77.97, 69.22, 49.02, and 57.30 pg/mL for P1-P4, respectively. This platform provides a companion diagnostic tool to identify patients with high TGF-β1⁺ EV burden, specifically those whose ``armor'' is likely to be overwhelmed, thereby guiding combination therapy or EV clearance strategies. In this retrospective cohort of four patients who all developed Grade 1 CRS, the EV-associated TGF-β1 signal rose before clinical onset in the retrospectively aligned trajectories; prospective validation in larger, higher-grade CRS cohorts is required in future studies.

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Sailing He, Faten Bashar Kamal Eddin, Abdur Rahim, Wen Lei, Qunyi Guo, Kaixin Zheng, Raheel Ahmed Janjua, and Wenda Luo, "A Magnetic Bead-Amplified SPR/SERS Dual-Modality Assay for EV-Associated TGF-β1 as a Companion Diagnostic for CAR-T Therapy," Progress In Electromagnetics Research Letters, Vol. 132, 43-53, 2026.
DOI:10.2528/PIERL26070501

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