Control of the activity of CAR-T cells within tumours via focused ultrasound

Yiqian Wu; Yahan Liu; Ziliang Huang; Xin Wang; Zhen Jin; Jiayi Li; Praopim Limsakul; Linshan Zhu; Molly Allen; Yijia Pan; Robert Bussell; Aaron Jacobson; Thomas Liu; Shu Chien; Yingxiao Wang

doi:10.1038/s41551-021-00779-w

Control of the activity of CAR-T cells within tumours via focused ultrasound

Nat Biomed Eng. 2021 Nov;5(11):1336-1347. doi: 10.1038/s41551-021-00779-w. Epub 2021 Aug 12.

Authors

Yiqian Wu^{1

2}, Yahan Liu^{2

3}, Ziliang Huang², Xin Wang¹, Zhen Jin⁴, Jiayi Li¹, Praopim Limsakul⁵, Linshan Zhu¹, Molly Allen¹, Yijia Pan¹, Robert Bussell⁶, Aaron Jacobson⁶, Thomas Liu⁶, Shu Chien^{7

8}, Yingxiao Wang^{9

10}

Affiliations

¹ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
² Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, USA.
³ Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China.
⁴ State Key Laboratory of Medical Genomics, Department of Haematology, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Division of Physical Science, Faculty of Science, Prince of Songkla University, Hat Yai, Thailand.
⁶ Center for Functional MRI, University of California, San Diego, La Jolla, CA, USA.
⁷ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA. shuchien@ucsd.edu.
⁸ Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, USA. shuchien@ucsd.edu.
⁹ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA. yiw015@eng.ucsd.edu.
¹⁰ Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, USA. yiw015@eng.ucsd.edu.

Abstract

Focused ultrasound can deliver energy safely and non-invasively into tissues at depths of centimetres. Here we show that the genetics and cellular functions of chimeric antigen receptor T cells (CAR-T cells) within tumours can be reversibly controlled by the heat generated by short pulses of focused ultrasound via a CAR cassette under the control of a promoter for the heat-shock protein. In mice with subcutaneous tumours, locally injected T cells with the inducible CAR and activated via focused ultrasound guided by magnetic resonance imaging mitigated on-target off-tumour activity and enhanced the suppression of tumour growth, compared with the performance of non-inducible CAR-T cells. Acoustogenetic control of the activation of engineered T cells may facilitate the design of safer cell therapies.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Cell- and Tissue-Based Therapy
Immunotherapy, Adoptive*
Mice
Neoplasms* / diagnostic imaging
Neoplasms* / therapy
T-Lymphocytes
Ultrasonic Therapy*

Abstract

Publication types

MeSH terms

Grants and funding