Nanosensors in clinical development of CAR-T cell immunotherapy

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Trang Anh Nguyen-Le - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Tabea Bartsch - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Robert Wodtke - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Florian Brandt - , Chair of Molecular Functional Materials (Faculty of Chemistry and Food Chemistry), Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Claudia Arndt - , Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden (Author)
  • Anja Feldmann - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Diana Isabel Sandoval Bojorquez - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Arnau Perez Roig - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Bergoi Ibarlucea - , Center for Advancing Electronics Dresden (cfaed) (Author)
  • Seungho Lee - , Pohang University of Science and Technology (Author)
  • Chan Ki Baek - , Pohang University of Science and Technology (Author)
  • Gianaurelio Cuniberti - , Center for Advancing Electronics Dresden (cfaed) (Author)
  • Ralf Bergmann - , Helmholtz-Zentrum Dresden-Rossendorf, Semmelweis University (Author)
  • Edinson Puentes-Cala - , Corporación para la Investigación de la Corrosión (CIC) (Author)
  • Javier Andrés Soto - , Universidad de Santander (Author)
  • Biji T. Kurien - , University of Oklahoma (Author)
  • Michael Bachmann - , Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden, German Cancer Research Center, German Cancer Consortium (DKTK) (Author)
  • Larysa Baraban - , Helmholtz-Zentrum Dresden-Rossendorf (Author)

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.

Details

Original languageEnglish
Article number114124
JournalBiosensors and Bioelectronics
Volume206
Publication statusPublished - 15 Jun 2022
Peer-reviewedYes

External IDs

PubMed 35272215