Ultrasound guides supercharged immune cells to only attack cancer

Bioengineers at the University of California San Diego have developed a cancer immunotherapy that pairs ultrasound with cancer-killing immune cells to destroy malignant tumors while sparing normal tissue. The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.

The work addresses a longstanding problem in the field of cancer immunotherapy: how to make chimeric antigen receptor (CAR) T-cell therapy safe and effective at treating solid tumors. CAR T-cell therapy is a promising new approach to treat cancer. It involves collecting a patient’s T cells and genetically engineering them to express special receptors, called CAR, on their surface that recognize specific antigens on cancer cells. The resulting CAR T cells are then infused back into the patient to find and attack cells that have the cancer antigens on their surface.

This therapy has worked well for the treatment of some blood cancers and lymphoma, but not against solid tumors. That’s because many of the target antigens on these tumors are also expressed on normal tissues and organs. This can cause toxic side effects that can kills cells—these effects are known as on-target, off-tumor toxicity.

CAR T cells are so potent that they may also attack normal tissues that are expressing the target antigens at low levels,” said first author Yiqian (Shirley) Wu, a project scientist in Wang’s lab.

The problem with standard CAR T cells is that they are always on—they are always expressing the CAR protein, so you cannot control their activation,” explained Wu.

To combat this issue, the team took standard CAR T cells and re-engineered them so that they only express the CAR protein when ultrasound energy is applied. This allowed the researchers to choose where and when the genes of CAR T cells get switched on.

We use ultrasound to successfully control CAR T cells directly in vivo for cancer immunotherapy,” said Wang, who is a faculty member of the Institute of Engineering in Medicine and the Center for Nano-ImmunoEngineering, both at UC San Diego. What’s exciting about the use of ultrasound, noted Wang, is that it can penetrate tens of centimeters beneath the skin, so this type of therapy has the potential to non-invasively treat tumors that are buried deep inside the body.

The team’s approach involves injecting the re-engineered CAR T cells into tumors in mice and then placing a small ultrasound transducer on an area of the skin that’s on top of the tumor to activate the CAR T cells. The transducer uses what’s called focused ultrasound beams to focus or concentrate short pulses of ultrasound energy at the tumor. This causes the tumor to heat up moderately—in this case, to a temperature of 43 degrees Celsius (109 degrees Fahrenheit)—without affecting the surrounding tissue. The CAR T cells in this study are equipped with a gene that produces the CAR protein only when exposed to heat. As a result, the CAR T cells only switch on where ultrasound is applied.

The research was published in the journal Nature Biomedical Engineering.

Super-powered Immune Cells Kill Cancer

Ground-breaking immune therapy promises to deliver vital evidence in the fight against cancer as researchers from the Centre for Cancer Biology in Australia open a new clinical trial using genetically engineered immune cells to treat solid cancers. The phase 1 clinical trial will test the feasibility and safety of CAR-T cellsgenetically modified white blood cells harvested from a patient’s own blood with the unique ability to directly attack and kill cancers – to treat advanced solid tumours including small cell lung cancer, sarcomas and triple negative breast cancer.

The new clinical trial will allow researchers to learn more about how CAR-T cells interact with solid tumours in the hope that this form of immune-based therapy may one day treat a wide range of different cancers. Led by the Centre for Cancer Biology – an alliance between University of South Australia (UniSA), the Central Adelaide Local Health Network (CALHN) and the Royal Adelaide Hospital, the trial is funded by Cancer Council’s Beat Cancer Project and sponsored by CALHN.

The research scientist in charge of manufacturing the CAR-T cell product and following the patients’ responses to treatment is UniSA’s Dr Tessa Gargett, a Cancer Council Beat Cancer Project Early Career Fellow from the Centre for Cancer Biology .She says the CAR-T immune therapy shows great potential for developing cancer treatments.

Chimeric antigen receptor (CAR) T cells are a promising new technology in the field of cancer immunotherapy,” Dr Gargett says. “Essentially, CAR-T cells are super-powered immune cells which work by enlisting and strengthening the power of a patient’s immune system to attack tumours. “They’ve had astounding results in treating some forms of chemotherapy-resistant blood cancers, but similar breakthroughs are yet to be achieved for solid cancers – that’s where this study comes in.”

Source: https://www.unisa.edu.au/