Control of the activity of CAR-T cells within tumours via focused ultrasound
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...
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| Veröffentlicht in: | Nature biomedical engineering 2021-11, Vol.5 (11), p.1336-1347 |
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| creator | Wu, Yiqian Liu, Yahan Huang, Ziliang Wang, Xin Jin, Zhen Li, Jiayi Limsakul, Praopim Zhu, Linshan Allen, Molly Pan, Yijia Bussell, Robert Jacobson, Aaron Liu, Thomas Chien, Shu Wang, Yingxiao |
| description | 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.
The activity of engineered T cells within tumours can be controlled via the heat generated by pulses of focused ultrasound by modifying the cells to express a chimeric antigen receptor under the control of a promoter for the heat-shock protein. |
| doi_str_mv | 10.1038/s41551-021-00779-w |
| format | Article |
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The activity of engineered T cells within tumours can be controlled via the heat generated by pulses of focused ultrasound by modifying the cells to express a chimeric antigen receptor under the control of a promoter for the heat-shock protein.</description><subject>13</subject><subject>13/1</subject><subject>13/21</subject><subject>13/31</subject><subject>38/44</subject><subject>38/77</subject><subject>59/5</subject><subject>631/553/552</subject><subject>631/67/1059/2325</subject><subject>64/60</subject><subject>Animals</subject><subject>Antigens</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Cell activation</subject><subject>Cell- and Tissue-Based Therapy</subject><subject>Chimeric antigen receptors</subject><subject>Heat</subject><subject>Heat shock proteins</subject><subject>Immunotherapy, Adoptive</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Magnetic resonance imaging</subject><subject>Mice</subject><subject>Neoplasms - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature biomedical engineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Yiqian</au><au>Liu, Yahan</au><au>Huang, Ziliang</au><au>Wang, Xin</au><au>Jin, Zhen</au><au>Li, Jiayi</au><au>Limsakul, Praopim</au><au>Zhu, Linshan</au><au>Allen, Molly</au><au>Pan, Yijia</au><au>Bussell, Robert</au><au>Jacobson, Aaron</au><au>Liu, Thomas</au><au>Chien, Shu</au><au>Wang, Yingxiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of the activity of CAR-T cells within tumours via focused ultrasound</atitle><jtitle>Nature biomedical engineering</jtitle><stitle>Nat Biomed Eng</stitle><addtitle>Nat Biomed Eng</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>5</volume><issue>11</issue><spage>1336</spage><epage>1347</epage><pages>1336-1347</pages><issn>2157-846X</issn><eissn>2157-846X</eissn><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.
The activity of engineered T cells within tumours can be controlled via the heat generated by pulses of focused ultrasound by modifying the cells to express a chimeric antigen receptor under the control of a promoter for the heat-shock protein.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34385696</pmid><doi>10.1038/s41551-021-00779-w</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-0332-285X</orcidid><orcidid>https://orcid.org/0000-0003-0265-326X</orcidid><orcidid>https://orcid.org/0000-0002-6313-6015</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/1 13/21 13/31 38/44 38/77 59/5 631/553/552 631/67/1059/2325 64/60 Animals Antigens Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Cell activation Cell- and Tissue-Based Therapy Chimeric antigen receptors Heat Heat shock proteins Immunotherapy, Adoptive Lymphocytes Lymphocytes T Magnetic resonance imaging Mice Neoplasms - diagnostic imaging Neoplasms - therapy Receptors Short pulses T-Lymphocytes Tumors Ultrasonic imaging Ultrasonic Therapy Ultrasound |
| title | Control of the activity of CAR-T cells within tumours via focused ultrasound |
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