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Ultrasound Boosts Cancer Gene Therapy

Cancer magnified

(PDPics, Pixabay)

25 June 2020. Ultrasound waves are shown in tests with lab mice to increase the uptake of a gene therapy that invokes the immune system in treating solid tumor cancers. Researchers from Stanford University in California describe their technique and results in the 9 June issue of Proceedings of the National Academy of Sciences (paid subscription required).

A team from the lab of Stanford biomedical engineering professor Katherine Ferrara is seeking more reliable and robust delivery methods for cancer therapies that invoke the immune system to attack tumors. Ferrara’s lab studies radiology techniques, originally designed for medical imaging, to better target treatments for cancer and other diseases. While immunotherapies are an important advance in cancer treatments, the researchers say they’ve had mixed success with patients, thus the need for methods to improve therapies that harness the immune system.

The PNAS paper describes the use of low-frequency ultrasound to both attack tumors and improve delivery of gene therapies for treating cancer. The team, led by Tali Ilovitsh, then a postdoctoral researcher in Ferrara’s lab, uses a technique with ultrasound waves to destroy most tumor cells, but also create pores in tumor cell membranes, which make them more susceptible to gene therapies. The pores are made with tiny gas bubbles guided to tumor cells with ultrasound, and then expand and explode, allowing the gene therapy to enter the tumor cell. The gene therapy in this case is a DNA fragment called a plasmid that codes for a cancer-killing cytokine or enzyme.

Ilovitsh, now a biomedical engineering lecturer at Tel Aviv University in Israel, explains that the small size of the micro-scale bubbles, about one-tenth the width of blood vessels and their balloon-like properties make them good delivery vehicles. “This process increases the transfer of substances from the blood vessels into the surrounding tissue,” says Ilovitsh in a Tel Aviv University statement. “We discovered that using lower frequencies than those applied previously, microbubbles can significantly expand, until they explode violently. We realized that this discovery could be used as a platform for cancer treatment and started to inject microbubbles into tumors directly.”

In tests with lab mice induced with breast cancer, the researchers discovered the ultrasound-guided and triggered microbubbles destroy about 80 percent of tumor cells on their own, but cancer treatments need to kill all of the cancer cells to prevent a relapse. “In order to prevent the remaining cancer cells to spread,” says Ilovitsh, “we needed to destroy all of the tumor cells. That is why we injected an immunotherapy gene alongside the microbubbles, which acts as a Trojan horse, and signaled the immune system to attack the cancer cell.”

Ilovitsh adds, “our mice had tumors on both sides of their bodies. Despite the fact that we conducted the treatment only on one side, the immune system attacked the distant side as well.”

The researchers believe the combination of ultrasound and microbubbles offers a technology that can be applied to other disorders, such as neurological diseases like Alzheimer’s and Parkinson’s diseases. “The blood-brain barrier does not allow for medications to penetrate through,” notes Ilovitsh, “but microbubbles can temporary open the barrier, enabling the arrival of the treatment to the target area without the need for an invasive surgical intervention.”

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