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
- WUGEN Announces Exclusive License Agreement for CAR-T Therapy Technologies from Washington University in St. Louis on November 13, 2018 at 6:56 am
"We hope that developing an effective "off-the-shelf" allogeneic CAR-T cell therapy will overcome challenges associated with fratricide and graft versus host disease." About WUGEN WUGEN Inc. is a biot... […]
- Children's Hospital of Philadelphia opens $75 million gene-therapy research lab on November 11, 2018 at 7:52 pm
An earlier version of CHOP's manufacturing facility developed tools crucial to producing CAR T-cell therapy, BioSpace reported. The facility also helped create Luxturna to treat a form of inherited bl... […]
- 'Game-changing' New Treatment for NHS Lymphoma Patients on November 9, 2018 at 7:49 am
In August, the European Commission approved the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel for treatment of pediatric and young adult relapsed or refractory B-cell acute lymphobla... […]
- A Patient's Journey To Join A CAR-T Cell Therapy Trial on November 8, 2018 at 2:31 pm
Cancer treatments are never easy on patients. Generally, those diagnosed with cancer are subject to multiple rounds of radiation and/or chemotherapy, both of which can have adverse effects on the body ... […]
- University of Pennsylvania cell therapy spinoff raises $38M on November 8, 2018 at 7:10 am
Milone, an associate professor of pathology and laboratory medicine and member of the Center for Cellular Immunotherapy since inception at Penn, is a co-inventor of Kymriah, the CAR-T cell therapy dev... […]
- New study sheds light on how CAR T cell therapy works on November 7, 2018 at 10:36 pm
Cancer remains the second-leading cause of death in the United States. This year, an estimated 1.7 million new cases will be diagnosed, with nearly 610,000 people expected to die from the disease, acc... […]
- CAR T-cell Therapies Moving to Outpatient Setting on November 7, 2018 at 1:30 pm
Axi-cel (axicabtagene ciloleucel; Yescarta) was the first CAR T-cell therapy, with an approval in October 2017. It was followed by tisagenlecleucel in May 2018, and one more candidate, liso-cel (lisoc... […]
- CAR-T Cell Therapy: Will First To Market Mean First To Disappoint? on November 5, 2018 at 10:49 am
Gilead and Novartis have launched the first two autologous CAR-T cell therapies. Combined, their first year revenues were less than $250 million. Significant manufacturing expansion plans have ... […]
- The Unlikely Story of Cancer's Most Promising New Therapy on November 4, 2018 at 2:46 pm
“I did the first CAR-T cell trials in humans in the mid-1990s,” June says. The treatment safely targeted HIV, but its effects were mild and the effort ended with the emergence of successful HIV drug c... […]
- Dr. Smith Discusses CAR T Cell Persistence in Myeloma on November 1, 2018 at 3:58 pm
Smith says that a way to advance CAR T-cell therapy for patients with myeloma is with novel CAR T-cell vectors that enhance the depth and persistence of responses for patients. In myeloma, multiple st... […]
via Google News and Bing News