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Nanosensors in clinical development of CAR-T cell immunotherapy.

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  • Additional Information
    • Source:
      Publisher: Elsevier Advanced Technology Country of Publication: England NLM ID: 9001289 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4235 (Electronic) Linking ISSN: 09565663 NLM ISO Abbreviation: Biosens Bioelectron Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Elsevier Advanced Technology
      Original Publication: [Barking, Essex, England] : Elsevier Applied Science, 1989-
    • Subject Terms:
    • Abstract:
      Immunotherapy using CAR-T cells is a new technological paradigm for cancer treatment. To avoid severe side effects and tumor escape variants observed for conventional CAR-T cells approach, adaptor CAR technologies are under development, where intermediate target modules redirect immune cells against cancer. In this work, silicon nanowire field-effect transistors are used to develop target modules for an optimized CAR-T cell operation. Focusing on a library of seven variants of E5B9 peptide that is used as CAR targeting epitope, we performed multiplexed binding tests using nanosensor chips. These peptides had been immobilized onto the sensor to compare the transistor signals upon titration with anti-La 5B9 antibodies. The correlation of binding affinities and sensor sensitivities enabled a selection of candidates for the interaction between CAR and target modules. An extremely low detection limit was observed for the sensor, down to femtomolar concentration, outperforming the current assay of the same purpose. Finally, the CAR T-cells redirection capability of selected peptides in target modules was proven successful in an in-vitro cytotoxicity assay. Our results open the perspective for the nanosensors to go beyond the early diagnostics in clinical cancer research towards developing and monitoring immunotherapeutic treatment, where the quantitative analysis with the standard techniques is limited.
      (Copyright © 2022 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: CAR-T cells; Cancer; Field-effect transistor; Immunotherapy; Nanosensor; Silicon nanowires
    • Publication Date:
      Date Created: 20220310 Date Completed: 20220414 Latest Revision: 20220414
    • Publication Date:
      20240104
    • Accession Number:
      10.1016/j.bios.2022.114124
    • Accession Number:
      35272215