A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.
There is a critical need to non-invasively and remotely manipulate cells at a distance, particularly for translational applications in animals and humans, researchers said.
The team developed an innovative approach to use mechanogenetics—a field of science that focuses on how physical forces and changes in the mechanical properties of cells and tissues influence gene expression—for the remote control of gene and cell activations. Researchers used ultrasound to mechanically perturb T cells, and then converted the mechanical signals into genetic control of cells.
In this study, researchers show how their remote-controlled mechanogenetics system can be used to engineer chimeric antigen receptor (CAR)-expressing T cells that can target and kill cancer cells. The engineered CAR-T cells have mechano-sensors and genetic transducing modules that can be remotely activated by ultrasound via microbubble amplification.
“CAR-T cell therapy is becoming a paradigm-shifting therapeutic approach for cancer treatment,” said bioengineering professor Peter Yingxiao Wang at the University of California San Diego. “However, major challenges remain before CAR-based immunotherapy can become widely adopted. For instance, the non-specific targeting of CAR-T cells against nonmalignant tissues can be life-threatening. This work could ultimately lead to an unprecedented precision and efficiency in CAR-T cell immunotherapy against solid tumors, while minimizing off-tumor toxicities.”
The team brings together the laboratories of professors Wang and Shu Chien, both bioengineering professors at the Jacobs School of Engineering and the Institute of Engineering in Medicine at UC San Diego, in collaboration with professors Kirk Shung of the University of Southern California and Michel Sadelain at Memorial Sloan Kettering Cancer Center in New York. Researchers present their findings in the Jan. 15 issue of the Proceedings of the National Academy of Sciences, with UC San Diego Ph.D. candidate Yijia Pan as the first author.
Researchers found that microbubbles conjugated to streptavidin can be coupled to the surface of a cell, where mechanosensitive Piezo1 ion channels are expressed. Upon exposure to ultrasound waves, microbubbles vibrate and mechanically stimulate Piezo1 ion channels to let calcium ions inside the cell. This triggers downstream pathways, including calcineurin activation, NFAT dephoshorylation and translocation into the nucleus. The nucleus-translocated NFAT can bind to upstream response elements of genetic transducing modules to initiate gene expression of chimeric antigen receptor (CAR) for the recognition and killing of target cancer cells.
The Latest on: CAR-T cell therapy
- Global CAR T Cell Therapy Market to 2026 - by Regions, Targeted Antigens, Clinical Trials/Study & Companies - ResearchAndMarkets.comon June 24, 2020 at 2:34 am
The "CAR T Cell Therapy Market Global Forecast by Regions, Targeted Antigens, Clinical Trials/Study, Companies" report has been added to ResearchAndMarkets.com's offering. This latest study report CAR ...
- Oncolytic virus-derived type I interferon restricts CAR T cell therapyon June 24, 2020 at 2:34 am
Oncolytic viruses promote an inflammatory response and elicit anti-tumor immunity. Here the authors show, unexpectedly, that the oncolytic virus, VSVIFNβ, induces type I interferon responses that, ...
- Producing CAR T cell therapy at a lower coston June 23, 2020 at 1:56 pm
T cell therapy is a new and in some cases highly effective form of immunotherapy to treat certain types of cancer of the blood and lymph system.
- CAR T Cell Therapy Market 2020 by Size, Share, Latest Global Trends, Top Key Players, Future Growth, Revenue Analysis, Demand Forecast To 2025on June 23, 2020 at 10:50 am
Global CAR T Cell Therapy Market is anticipated to reach over USD 2.99 Billion by 2025 According to a new research published by Polaris Market Research. The CAR T therapy uses the patient's own immune ...
- CAR T cell therapy: Potential for considerable savingson June 23, 2020 at 9:06 am
T cell therapy is a new and in some cases highly effective form of immunotherapy to treat certain types of cancer of the blood and lymph system. This promising treatment comes at a cost, however: The ...
- Sana Biotechnology raises more than $700M for cell, gene therapy effortson June 23, 2020 at 7:26 am
The co-founders of the company include Hans Bishop, who founded Juno Therapeutics - one of the earliest commercial developers of CAR-T cell therapy technology - in 2013.
- Insight to CV Risks of CAR T-Cell Therapyon June 17, 2020 at 3:37 pm
MACE often occurred within the same time frame as cytokine release syndrome (CRS), a recognized and potentially serious complication of CAR T-cell therapy. Patients who had MACE tended to be younger ...
- Agenus and AgenTus to Participate in a Panel Presentation on Cell Therapy at the Raymond James Virtual Human Health Innovation Conferenceon June 17, 2020 at 8:06 am
PRNewswire/ -- Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, adoptive cell therapies ...
- Zaia Draws on Decades of Innovation in Infectious Disease for Breakthroughs in Gene Therapyon June 16, 2020 at 6:23 pm
Known as a gene therapy pioneer, Zaia has spent almost 40 years at City of Hope, in Duarte, California. He was first drawn by the promise of studying cytomegalovirus. Over the decades, his ...
- CAR-T Therapy Market Outlook to 2030 by Target Antigen, Application, Region, Country and Companyon June 16, 2020 at 4:15 am
PRNewswire/ -- The "CAR-T Therapy Market Global Report 2020-30" report has been added to ResearchAndMarkets.com's offering. The global CAR-T therapy market was worth $611.31 million in 2019. It is ...
via Google News and Bing News