Nanosensors in clinical development of CAR-T cell immunotherapy

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作   者：

Trang Anh Nguyen-Le;  Bartsch, Tabea;  Wodtke, Robert;  Brandt, Florian;  Arndt, Claudia;  Feldmann, Anja;  Bojorquez, Diana Isabel Sandoval;  Roig, Arnau Perez;  Ibarlucea, Bergoi;  Lee, Seungho;  Baek, Chan-Ki;  Cuniberti, Gianaurelio;  Bergmann, Ralf;  Puentes-Cala, Edinson;  Soto, Javier Andres;  Kurien, Biji T.;  Bachmann, Michael;  Baraban, Larysa; 

作者机构：

Univ Santander;  Tech Univ Dresden;  Pohang Univ Sci & Technol;  Helmholtz Zentrum Dresden Rossendorf eV HZDR;  Oklahoma Med Res Fdn;  Corp Invest Corros CIC; 

关键词：

CANCER-CELLS;  CD8(+);  PROTEIN;  CAR-T cells;  Field-effect transistor;  TUMOR-CELLS;  SENSORS;  Silicon nanowires;  Nanosensor;  PLATFORM;  Immunotherapy;  KINETICS;  CD4(+);  Cancer;  LYMPHOCYTES; 

期刊名称：

Biosensors & Bioelectronics: The International Journal for the Professional Involved with Research, Technology and Applications of Biosensers and Related Devices

i s s n：

0956-5663

年卷期：

2022 年 206 卷

页   码：

ARTN 114124-

页   码：

摘   要：

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.