A Bionic Slice of Life

The pandemic had many downsides but for Professor Nancy Man Kwan, Chair Professor of Transplant Oncology and Immunology from the Department of Surgery and an expert in liver transplantation and disease, it offered a silver lining. Forced to halt her visits to conferences and meetings around the world and to stay put in Hong Kong, she used the free time to develop innovative technology that makes precision treatment possible for liver cancer patients and opens the path to new drug development.

The Bionic Liver-in-Cube was co-developed with engineer Professor Lu Jian at the City University of Hong Kong. It involves taking samples of liver patients’ tumours and the surrounding area, and bioprinting them into a cube where doctors can test out the best treatment for patients.

Such a device could offer much-needed hope to liver patients, who each tends to have different tumours and immune microenvironments that respond differently to treatment, making outcomes unpredictable even with the same drugs. About 80 per cent of the 1,800 new liver cancer cases diagnosed in Hong Kong each year are already at an advanced stage, and about 1,500 succumb to the disease annually. The lack of precision drug-screening means patients often undergo multiple treatment failures in the search for the right drug.

“Our invention could provide speedy and precise treatment options in the best interests of patients and significantly improve their quality of life by promoting early diagnosis and treatment of cancer and liver disease,” Professor Man said.

Three innovations

The team developed three core technologies. One separates the cells and matrix protein by simultaneously extracting non-cancerous liver cells, tumour cells, immune cells and matrix proteins from the tissue of the liver patient. These can all differ from patient to patient, for instance, some may have better function of the immune T cells than others. This approach enables the scientists to precisely characterise the tumour, such as the number of cells, immune status and tissue stiffness, and quickly screen drugs to find the most effective treatment and determine possible side effects.

The second innovation uses 3D bioprinting technology to fabricate a new model of the patient’s tumour environment that combines their normal tissue, tumour tissue and vascular structure within the Liver-in-Cube.

The third is a unique microvascular system within the model to keep the environment fresh and allow for continuous drug tests to be performed and to evaluate the effects of different therapies on the bench.

“We can select the drug treatments, including immunotherapy for individual patients, because we can test it with the patient’s immune cells in place,” said Professor Man. “This could allow patients to quickly receive the best treatments for them with the least adverse effects and reduced chance of recurrence.”

Before that can happen, though, regulatory approval is needed and that requires more data. Professor Man’s team currently are collecting about five to eight samples from patients each month for the Liver in Cube. She has also been in contact with hospitals around the region, including the University of Hong Kong–Shenzhen Hospital, which are interested in participating.

“We are currently doing a clinical feasibility study. That means we are collecting patient samples, doing the printing, and in the laboratory, we are trying different treatments. When we have enough data showing there is a match with patients’ real situations, we can then do a clinical trial using the results to guide drug selection for future patients,” she said.

Applicable to other cancers

The technology is also applicable to different cancer types and they recently started collaborating with a neurosurgeon on brain cancer. They have also started using the technology to look at different therapeutics, which is under patent application. A key attraction is that the Liver-in-Cube is much cheaper than organoids, which cannot mimic the immune system.

Professor Man’s research is built on more than 20 years of experience in the cancer immune environment. As a surgeon-scientist, she aims to reduce cancer recurrence rates among both those who retain their liver and those who have liver transplants. She hopes the Liver- in-Cube will also help uncover the mechanism for tumour recurrence, as well as possible treatments.

“The dream is that we could have a tailor-made printing machine in the operating theatre, where we could directly print the material from the patient, then quickly do a drug selection right after surgery. So even before the patient goes home, we would have an individual regimen for them. That is the dream, but we start with the Liver- in-Cube first. At least we have great potential for drug selection and new drug development,” she said.