New modalities for treatment of certain cancers has rapidly evolved in the last few years, specifically harnessing the immune system to directly target tumor cells. The basis of the work is to engineer the patient’s own T cells to create an enhanced anticancer activity targeted to a specific marker on the tumor cell. This is accomplished by harvesting peripheral blood mononuclear cells from the patient to produce a chimeric antigen T receptor (CAR-T) which recognizes a tumor marker, expanding them to reach a therapeutic number of cells and infusing them back into the patient. While this has worked very well in treating a number of cancers, particularly B-cell malignancies, it is only in a state of infancy for treatment of solid tumors.
Researchers at UC San Diego have developed a novel strategy to treat solid tumors. CAR-T cells were engineered to express a mechanosensitive channel, Piezol1 and a calcium responsive construct containing the chimeric antigen receptor (CARs). The mechanotransductive protein also carries an external microbubble, whereby when ultrasound is applied can move the bead, which stimulates the protein, to upregulate translation of the CAR genetic sequence, which produces the therapeutic effect.
This invention may be useful for the safe and noninvasive delivery of mechanical energy into small volumes of tissue deep inside the body to generate an intracellular response of signal or therapeutic outcome.
Noninvasive technique capable of deep tissue penetration.
Ultrasound stimulation HEK cells expressing Piezol and coupled to microtubules caused calcium and gene activation in these cells.
A provisional patent has been submitted.