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

FDA grants priority review to Roche's cancer immun…

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the US Food and Drug Administration (FDA) has accepted the company's supplemental Biologics License Application (sBLA) a...

Kymriah® (tisagenlecleucel), first-in-class CAR-T …

Novartis today announced the US Food and Drug Administration (FDA) has approved Kymriah® (tisagenlecleucel) suspension for intravenous infusion for its second indication ...

Daily aspirin linked to higher risk in men

Men who take once-daily aspirin have nearly double the risk of melanoma compared to men who are not exposed to daily aspirin, reports a new Northwestern Medicine study. W...

New leads on treating dementia and Alzheimer's

A new research study by scientists in Australia and the US provides an explanation for why clinical trials of drugs reducing proteins in the brain that were thought to ca...

Roche reports a strong start in 2018

Roche (SIX: RO, ROG; OTCQX: RHHBY) has announced that in the first three months of 2018, Group sales rose 6% to CHF 13.6 billion. Sales in the Pharmaceuticals Division in...

To treat pain, you need to treat the patient

People in chronic pain are some of the most difficult patients to treat. They have complex circumstances that medicine can't always remedy. Pain can be amplified, by depr...

Novo Nordisk participates in new research project …

Within the newly started European research project Hypo-RESOLVE, 23 leading international players from academia, industry and civil society have joined forces to find bet...

Chemical octopus catches sneaky cancer clues, trac…

Cancer drops sparse chemical hints of its presence early on, but unfortunately, many of them are in a class of biochemicals that could not be detected thoroughly, until n...

Alcon Cares Project 100 commits to reducing catara…

Alcon, the global leader in eye care and a division of Novartis, has announced Alcon Cares Project 100, which aims to reduce cataract blindness by providing equipment to ...

FDA approves novel preventive treatment for migrai…

The U.S. Food and Drug Administration today approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. The treatment is given by once-monthly se...

First clues to the causes of multiple sclerosis

Multiple sclerosis, which affects 1 in 1,000 people, is frequently characterised by relapses associated with variable functional impairments including among others vision...

Doctors in US and Canada launch sweeping pharmaceu…

The skyrocketing cost of prescription drugs is one of the biggest concerns for American voters. However, in his proposal last Friday, President Donald Trump failed to off...