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Mechanogenetics for the remote and non‐invasive control of cancer immunotherapy
Author(s) -
Pan Yijia,
Yoon Sangpil,
Sun Jie,
Huang Ziliang,
Lee Changyang,
Allen Molly,
Wu Yiqian,
Chang YaJu,
Sadelain Michel,
Shung K. Kirk,
Chien Shu,
Wang Yingxiao
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.674.24
Subject(s) - cancer immunotherapy , immunotherapy , peripheral blood mononuclear cell , computational biology , cancer research , cancer , biology , in vitro , genetics
While cell‐based immunotherapy, especially chimeric antigen receptor (CAR)‐expressing T cells, is becoming a paradigm‐shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and non‐invasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK cells to convert the ultrasound‐activated Piezo1 into transcriptional activities. We have further engineered Jurkat T cell line and primary T cells (periphery blood mononuclear cells, PBMCs) to remotely sense the ultrasound wave and transduce it into transcriptional activation for the CAR expression to recognize and eradicate target tumor cells. This approach is modular and can be extended for remote‐controlled activation of different cell types with a high spatiotemporal precision for therapeutic applications. Support or Funding Information This work is supported by grants from NIH HL121365, GM125379 (S.C. and Y. Wang), CA204704 and CA209629 (Y. Wang), NSF CBET1360341, DMS1361421 (Y. Wang and S.L.), and the Beckman Laser Institute Foundation. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Design of synthetic genetic circuits remotely activatable by ultrasoundThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .