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
U-M Rogel Cancer Center First in Michigan to Offer All FDA Approved Car T-Cell Therapies
on May 23, 2018 at 12:41 pm
Michigan Medicine has been on the front lines of CAR T-cell therapy, participating in the pivotal trials that led to the approval of the first FDA-approved CAR T-cell therapy in 2017. “This is the dawn of a new and exciting era in cancer therapy,” says ... […]
Cesca Therapeutics Snags Bullish HC Wainwright Initiation On CAR-T Opportunity
on May 23, 2018 at 11:47 am
CAR-T-cell therapy is a method of treating cancer by using a patient's immune system cells — T cells — which are then modified by adding a gene in the lab for a special chimeric antigen receptor, or CAR, to attack cancer cells. CAR binds to a certain ... […]
Cesca Therapeutics’ Chief Technology Officer, Phil Coelho, Provides Deep Dive into the CAR-T Manufacturing Process in Cell & Gene Therapy
on May 23, 2018 at 6:33 am
RANCHO CORDOVA, Calif., May 23, 2018 (GLOBE NEWSWIRE) -- Cesca Therapeutics Inc. (“Cesca” or the “Company”) (KOOL), a market leader in automated cell processing and point-of-care, autologous cell-based therapies, today announced that Phil Coelho ... […]
Global T-Cell Immunotherapy Market Growing Rapidly In Coming Years For Advanced Stage Cancer Treatment
on May 23, 2018 at 5:56 am
Recently, the USFDA approved two T-cell Immunotherapies for the treatment of cancer. The approved therapies belong to the class of CAR T-cell Immunotherapies. CAR T-cell therapies are the most researched type of therapy as they have shown exceptional ... […]
Lupagen & Humanigen to explore point-of-care CAR-T therapy
on May 22, 2018 at 4:23 am
DALLAS, May 22, 2018 /PRNewswire/ -- Lupagen, Inc. (www.lupagen.com), a medical device company developing first-in-class cell and gene therapy delivery technologies for CAR-T, gene editing and immunotherapy products, today announced the intent to explore ... […]
Interview with CAR T cell expert Dr. Michel Sadelain in Human Gene Therapy
on May 21, 2018 at 7:58 am
New Rochelle, NY, May 18, 2018--Michel Sadelain, MD, PhD, Director, Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center in New York City, offers a fasci-nating perspective on the remarkable progress being made in the field of chimeric ... […]
Cellectis: Will Focus On Universal CAR-T Payoff?
on May 21, 2018 at 7:24 am
Gene editing, gene therapy, and cell therapy have entered our collective conscious. One particularly compelling approach called Universal CAR-T cell therapy is the topic for this article: What is it and who is emerging as the leader in the precise ... […]
CAR T-Cell Therapy, Checkpoint Inhibitors Making Waves Across Hematologic Malignancies
on May 18, 2018 at 11:29 am
The future is bright for the treatment of patients with hematologic malignancies, most recently due to advancements in chimeric antigen receptor (CAR) T-cell therapy and immune checkpoint inhibitors, said Anas Younes, MD. Tisagenlecleucel (Kymriah) was ... […]
CAR Therapy for Solid Tumors Passes Early Milestone
on May 17, 2018 at 9:03 am
Scientists at Memorial Sloan Kettering are investigating ways to develop effective CAR T cell therapies for solid tumors. Preliminary results from a clinical trial in people with mesothelioma indicate that an experimental CAR therapy is safe. Chimeric ... […]
Viewpoint: China has the upper hand in cancer cell therapy
on May 17, 2018 at 7:42 am
Cheers went up last August when the U.S. Food and Drug Administration approved the world’s first CAR-T cancer cell treatment, Novartis’ Kymriah, and again in October when it approved Gilead’s CAR-T treatment for non-Hodgkin's lymphoma. In CAR-T ... […]
via Google News and Bing News