An Unusual Approach To Fighting Cancer

Cancer treatment has undergone a revolution in recent years, with many innovative therapies coming onto the market. This is particularly true for cancer therapies that use a person’s immune system to target tumors. For example, CAR T-cell therapies – which involve engineering a patient’s immune cells to recognize and kill cancer cells before reinjecting them back into the body to target the cancer – have made a huge impact.

Sadly, only a lucky few patients get access to immunotherapy, even today. This kind of treatment does not work for every kind of cancer. Even for those that can be targeted in this way, toxic side effects are a real risk.

Many cancer patients are restricted to treatment with more old-fashioned chemotherapy drugs, which are known for making patients feel even sicker. Alternatively, or additionally, they might need radiation therapy, a pathway that is also associated with negative effects such as hair loss.

There is a need for new approaches and techniques to treat more cancer patients quickly and effectively with minimal side effects. Tali Ilovitsh, PhD, is an assistant professor in the department of biomedical engineering at Tel Aviv University Israel – last year she was selected to be on the Forbes Israel 30 under 30 list. While working in the US with Katherine Ferrara, PhD, a professor of radiology at Stanford University, she discovered a technique that could be used to treat cancer using ultrasound and microbubbles.

“Microbubbles are microscopic bubbles filled with gas, with a diameter as small as one tenth of a blood vessel. These tiny gas-filled spheres are approved by the US FDA, and are typically used to enhance vascular imaging in patients,” Ilovitsh explained.

“At certain frequencies and pressures, sound waves cause the microbubbles to act like balloons: they expand and contract periodically… 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.”

The researchers hope to test their technique in humans soon, but in this early study they used a mouse model of breast cancer. They injected microbubbles into breast tumors in mice, before exposing the mice to low frequency (250 kHz) ultrasound waves to ‘activate’ the bubbles to explode. This process killed 80% of the targeted tumor cells.

However, this does not completely solve the problem, as some tumor cells are left to multiply again. So Ilovitsh, Ferrara and their fellow researchers came up with a second step to get rid of the remaining cells.

A combination of ultrasound and microbubbles can be used to make small holes in the surface of cells to allow drugs or other substances to pass through. This is also one method of getting genes into cells to help treat or prevent disease, so-called ‘gene therapy’. This method has been used in animal models before, for example to promote bone healing, but using it to help treat cancer has proved challenging.

Ilovitsh and Ferrara injected genes that would trigger the immune system to destroy the tumor cells at the same time as they injected the mice with the microbubbles. When the animals were exposed to the ultrasound it allowed the gene to enter the undestroyed tumor cells. This technique effectively alerts the immune system to the remaining cancer cells and helps it to attack and get rid of them.

“The new treatment platform is designed to deliver a one-two punch. First, the microbubbles attack cancer cells, then a gene beckons immune cells to further pummel the tumor,” said Ferrara.

Ilovitsh explained that this immune reaction was more effective than they initially thought it would be. “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.”

Although these results are encouraging, the microbubble treatment is not quite ready for use in humans, according to Ferrara. More refining of the second ‘gene therapy’ step is needed before it can get to the clinic.

One big advantage of this type of therapy is that the ultrasound application is non invasive and the use of microbubbles limits any healthy tissue damage that might occur if only ultrasound was used.  If the team can get their technique to work in humans this would be a big plus compared to regular chemo and radiotherapy.

Using ultrasound to get through barriers in the body has a lot of potential for treating brain cancers and other neurological conditions, as it can be used to help treatment to get through the blood—brain barrier. Normally, this barrier makes treating brain diseases hard, as it is difficult to get drugs or treatments through it and close enough to the affected area of the brain to be effective.

“The blood-brain barrier does not allow for medications to penetrate through, 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,” said Ilovitsh, who wants to use their microbubble technique to target brain diseases in the future.

Others are already starting to exploit this space. Scientists at the University of Virginia recently developed a similar technique to target glioblastoma, an aggressive brain cancer.

French biotech CarThera is also using ultrasound to target brain cancers including glioblastoma. It makes specialized ultrasound devices that can be used to open the blood—brain barrier and allow drugs to reach their targets more easily.

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