Jan 172018

A schematic drawing of ultrasound-induced cell activation and gene expression.

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.

Learn more: Researchers Develop a Remote-Controlled Cancer Immunotherapy System


The Latest on: CAR-T cell therapy
  • Breakthrough cancer therapy raises tough questions
    on February 22, 2018 at 6:27 pm

    This isn’t fantasy. This is the profile of Novartis’ Kymriah, the first-of-its-kind CAR T-cell therapy. No wonder it has inspired awe, as well as deep concerns, that the benefits have been overstated and overpriced. Novartis partnered with the ... […]

  • Global CAR T Cell Therapy Market 2018 Industry Trend and Forecast 2025
    on February 21, 2018 at 10:26 pm

    The report covers the analysis and forecast of the CAR T cell therapy market on global as well as regional level. The study provides historic data of 2016 along with the forecast for the period between 2017 and 2025 based on revenue (US$ Million). […]

  • Cancer Vaccines May Overhaul Cancer Therapy in the Next Decade
    on February 21, 2018 at 7:00 am

    or customize each patient’s T cells as in CAR-T. Even better: both molecules in the vaccine are already approved individually for human use. Levy is now recruiting about 15 patients with lymphoma to test the therapy. If it works, patients with multiple ... […]

  • How Celgene Hopes to Cash In on CAR-T
    on February 17, 2018 at 9:48 am

    Chimeric antigen T-cell therapy (CAR-T) is an important new approach to battling blood cancer, and while it's too soon to say what company will develop an approved treatment first, Celgene (NASDAQ: CELG) has a good shot at coming out on top. In January ... […]

  • CAR-T therapy saves life of cancer researcher
    on February 14, 2018 at 10:49 pm

    The clinical trial was for a groundbreaking new "living drug" called chimeric antigen receptor T-cell therapy or CAR-T therapy. CAR-T is a technique that involves gathering T cells (a type of immune cell) from the cancer patient's blood, re-engineering ... […]

  • Poseida Therapeutics Presents Stem Cell Memory CAR-T Therapy for Prostate Cancer at 2018 Keystone Symposia on Emerging Cellular Therapies
    on February 14, 2018 at 5:02 am

    SAN DIEGO, Feb. 14, 2018 (GLOBE NEWSWIRE) -- Poseida Therapeutics Inc. (“Poseida”), a San Diego-based company translating best-in-class gene engineering technologies into lifesaving cell therapies, presented preclinical data on P-PSMA-101 at the 2018 ... […]

  • UCLA Health certified to offer cancer cell modification therapy
    on February 13, 2018 at 11:48 pm

    ... is a form of chimeric antigen receptor T-cell therapy, in which a synthetic gene is added to T cells that recognize infectious substances and mount an immune response. The added gene enables CAR T cells to recognize cancer cells. Joshua Sasine, a ... […]

  • CAR T-cell therapy promising across age groups in refractory ALL setting
    on February 13, 2018 at 4:23 am

    medwireNews: Autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy leads to high remission rates and durable responses in children, young adults, and adults with refractory acute lymphoblastic leukemia (ALL), indicate two reports ... […]

  • New research into CAR-T cell therapy could extend its use to solid cancers
    on February 12, 2018 at 8:17 pm

    New research into CAR-T cell therapy by researchers at the Walter and Eliza Hall Institute of Medical Research (WEHI) has revealed crucial mechanisms that could help the immunotherapy technique, which is currently only effective against blood cancers, be ... […]

via Google News and Bing News

Other Interesting Posts

Leave a Reply

%d bloggers like this: