Lymphocyte puller
A group of American researchers has developed an innovative approach to the use of mechanogenetics – the field of science of the influence of physical forces and changes in the mechanical properties of cells and tissues on gene expression. The aim of the work was to manipulate genes at a distance. To excite T-lymphocytes, scientists used ultrasound, and then transformed mechanical signals to control the expression of target genes.
This study demonstrates the use of ultrasound remote control of T cells producing chimeric antigen receptor (chimeric antigen receptor, CAR). CAR is a protein that provides recognition and destruction of cancer cells by T–lymphocytes.
T-lymphocytes with CAR have mechanical sensors and genetically transformable modules that can be remotely activated by ultrasound by enhancing the mobility of microbubbles.
Scheme of ultrasonic cell activation and gene expression
Cell therapy with CAR-T lymphocytes is currently becoming the main approach for the treatment of cancer. Nevertheless, there remain challenges that need to be overcome for the widespread use of this type of immunotherapy. For example, non-specific targeting of CAR-T lymphocytes on non-malignant tissues can be life-threatening for the patient. This study will help improve the accuracy and effectiveness of CAR-T lymphocytes in the fight against solid tumors, minimizing damage to healthy tissues.
The group included researchers from the Jacobs School of Engineering, the Institute of Engineering in Medicine at the University of California, San Diego, the University of Southern California and the Cancer Center in New York. They found that microbubbles conjugated with streptavidin can be placed on the cell surface with mechanosensitive piezo-1-ion channels. Under the influence of ultrasonic waves, the microbubbles begin to vibrate and thus stimulate piezoionic channels to pass calcium ions into the cell.
This triggers a chain of processes, including calcineurin activation, dephosphorylation of NFAT (nuclear activation factor of T cells) and its translocation into the nucleus. The movement of NFAT into the cell nucleus causes genetic transformations leading to the expression of the gene responsible for CAR synthesis. As a result, T-lymphocytes acquire the ability to recognize and destroy cancer cells.
Article by Yijia Pan et al. Mechanogenetics for the remote and non-invasive control of cancer immunotherapy is published in the journal PNAS.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on the materials of the UC San Diego News Center: Researchers Develop a Remote-Controlled Cancer Immunotherapy System.