Two-dimensional label-free affinity analysis of tumor-specific CD8 T cells with a biomimetic plasmonic sensor

Publication year: 2018
Authors: Soler M. 1, Li X. 1, John-Herpin A. 1, Schmidt J. 2, Coukos G. 2, Altug H. 1
Affiliations:

1- Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2 - Lausanne Branch - Ludwig Institute for Cancer Research, and Department of Oncology, University of Lausanne (UNIL), CH-1007 Lausanne, Switzerland

Published in: ACS Sensors, 2018
doi: 10.1021/acssensors.8b00523

The screening and analysis of T cells functional avidity for specific tumor-associated antigens is crucial for the development of personalized immunotherapies against cancer. The affinity and kinetics of a T cell receptor (TCR) binding to the peptide-major histocompatibility complex (pMHC), expressed on tumor or antigen-presenting cells, have shown major implications in T cell activation and effector functions. We introduce an innovative methodology for the two-dimensional affinity analysis of TCR-pMHC in a label-free configuration by employing a multiparametric Surface Plasmon Resonance biosensor (MP-SPR) functionalized with artificial cell membranes. The biomimetic scaffold created with planar lipid bilayers is able to efficiently capture the specific and intact tumor-specific T cells and monitor the formation of the immunological synapse in situ. We have achieved excellent limits of detection for in-flow cell capturing, up to 2 orders of magnitude below the current state-of-the-art for plasmonic sensing. We demonstrate the accuracy and selectivity of our sensor for the analysis of CD8+ T cells bioengineered with TCR of incremental affinities specific for the HLA-A0201/NY-ESO-I157–165 pMHC complex. The study confirmed the significance of providing a biomimetic microenvironment, compared to the traditional molecular analysis, and showed fine agreement with previous results employing flow cytometry. Our methodology is reliable and versatile; thus, it can be applied to more sophisticated photonic and nanoplasmonic technologies for the screening of multiple cell types and boost the development of novel treatments for cancer.


MP-SPR keywords: artificial cell membrane, biosensor for cancer research, biotinylated peptide-major histocompatibility complex immobilized using streptavidin on lipids, immobilization of anti-CD3 antibody using amine coupling on lipids, interaction affinity, layer thickness based on three wavelength analysis, live T-cell detection, supported lipid bilayer on SiO2 sensor surface