Researchers Develop a Remote-Controlled Cancer Immunotherapy System

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.

Pan Y, Yoon S, Sun J, Huang Z, Lee C, Allen M, Wu Y, Chang Y-J, Sadelain M, Shung KK, Chien S, Wang Y.
Mechanogenetics for the remote and non-invasive control of cancer immunotherapy.
Proc Natl Acad Sci USA, 2017. doi: http://dx.doi.org/10.1073/pnas.1714900115.

Most Popular Now

MSD Innovation Factory Selects 3 Compani…

Throughout the MSD Innovation Factory, MSD launched 7 health-related challenges to award the three most outstanding solutions. Blendarsys, Symptoma and Grupo Pulso are the winners out of 100 proposals. The...

Using Virtual Reality to Identify Brain …

Virtual reality is helping neuroscientists at the University of California, Davis, get new insight into how different brain areas assemble memories in context. In a study published Jan. 18 in...

People with Tetraplegia Gain Rapid Use o…

For a brain-computer interface (BCI) to be truly useful for a person with tetraplegia, it should be ready whenever it's needed, with minimal expert intervention, including the very first time...

East Lancashire Hospitals Chooses Cerner…

East Lancashire Hospitals NHS Trust (ELHT) has chosen global health information technology leader Cerner as its Preferred Supplier of a new clinical information system that will help to improve the...

Hamlyn Centre Announces Grant from Bill …

The Hamlyn Centre at Imperial College London today announces the award of a grant from the Bill & Melinda Gates Foundation, to accelerate research into new integrated technology systems for...

Philips Debuts Fully Integrated Suite o…

Royal Philips (NYSE: PHG, AEX: PHIA), a global leader in health technology, announced the launch of its next-generation Patient Monitoring solution in the U.S. The enterprise-wide system consists of bedside...

Liverpool Awards Contract to Docobo

One of the best-known users of telehealth in England has awarded a contract to Docobo to significantly expand its service over the next three years. NHS Liverpool Clinical Commissioning Group...

Augmented Reality System Lets Doctors Se…

New technology is bringing the power of augmented reality into clinical practice. The system, called ProjectDR, allows medical images such as CT scans and MRI data to be displayed directly...

Assessing Health Technology in the EU: C…

European Commission has put forward a proposal to boost cooperation amongst EU Member States for assessing health technology. Greater transparency will empower patients, by ensuring their access to information on...

ProEmpower Releases Call for Tenders to …

The ProEmpower procurers are looking for a diabetes management solution that will tackle the unmet needs in the current treatment of diabetes such as the fragmentation in today’s healthcare systems...

Biosensors Will Be Inexpensive, Do More…

When it comes to biometric sensors, human skin isn't an ally. It's an obstacle. The University of Cincinnati is developing cutting-edge methods to overcome this barrier without compromising the skin...