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

Forxiga receives positive EU CHMP opinion for the …

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended a new indication for the marketing authorisation of Forxi...

US FDA grants Breakthrough Therapy Designation for…

AstraZeneca and its global biologics research and development arm, MedImmune, today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Ther...

New pill can deliver insulin

An MIT-led research team has developed a drug capsule that could be used to deliver oral doses of insulin, potentially replacing the injections that people with type 2 di...

Merck to expand US biopharmaceutical R&D facil…

Merck, a leading science and technology company, today announced a $70 million investment to expand its state of the art research and development (R&D) facility in Biller...

Pfizer receives positive CHMP opinion for Vizimpro…

Pfizer today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending V...

Cannabinoid compounds may inhibit growth of colon …

Medical marijuana has gained attention in recent years for its potential to relieve pain and short-term anxiety and depression. Now, Penn State College of Medicine resear...

Merck Granted U.S. Patent for novel combination of…

Merck, a leading science and technology company, today announced that it has been granted Patent No. US 10,193,695 by the United States Patent and Trademark Office (USPTO...

Simple drug combination creates new neurons from n…

A simple drug cocktail that converts cells neighboring damaged neurons into functional new neurons could potentially be used to treat stroke, Alzheimer's disease, and bra...

The Union for International Cancer Control and Pfi…

In conjunction with World Cancer Day, the Union for International Cancer Control (UICC) and Pfizer Inc. announce the third round of the Seeding Progress And Resources for...

Pfizer and Lilly announce top-line results from se…

Pfizer Inc. (NYSE:PFE) and Eli Lilly and Company (NYSE:LLY) today announced positive top-line results from a Phase 3 study evaluating tanezumab 2.5 mg or 5 mg in patients...

Merck and Tencent announce collaboration on intell…

Merck, a leading science and technology company, signed a strategic collaboration agreement with Tencent, a leading provider of Internet value added services. The collabo...

New insight into cell receptors opens the way for …

New research on how cancer mutations influence a certain type of receptor on the cell membrane opens the way for the development of tailored drugs for certain cancers, su...