Liver cancer in the crosshairs
Nathalie Wong’s 20-year quest seeks to harness the patient’s own immune defences
14 January 2026
This is the last part of a series in which CUHK in Focus talks to leaders of six CUHK projects selected for the second round of the Hong Kong government’s Research, Academic and Industry Sectors One-plus (RAISe+) Scheme. It provides up to HK$100 million to each approved project, helping local universities transform, realise and commercialise their research and development (R&D) outcomes. Including the seven that were chosen in 2024, a total of 13 CUHK projects have received funding from the Scheme so far, the most among local institutions.
Professor Nathalie Wong is on a crusade against liver cancer. Her tool of choice is a certain type of white blood cells which, when genetically modified, may be made to recognise and attack cancerous cells. It is a way of mobilising the patients’ own immune system to battle the disease ravaging their body, an illness that is the sixth most common cancer worldwide and afflicts Chinese and Southeast Asians in particular.
To deal with the critical public health challenge, the Director of Surgical Sciences sees potential in adapting the innovative “chimeric antigen receptor (CAR)-T cell” immunotherapy from blood cancer treatment to fighting solid tumours.
“CAR-T cell therapy is an area worth exploring due to its highly promising results in treating blood cancersHowever, its application against solid tumours remains limited. Our project embarks on this area and aims to address existing challenges, and we are hopeful we can achieve a positive outcome.”
In the genetic engineering process, a new gene construct is introduced into the patients’ T cells, or T lymphocytes, which are part of the body’s natural defences. For the treatment to work, the modified CAR-T cells must be able to identify the marker – the specific protein make-up on the membrane of the target cancer cells – and eradicate them.
Discovering the first-of-its-kind liver cancer marker
For more than two decades, Professor Wong has set her mind on pioneering research in the genomics and tumour biology of liver cancer. Her team is at the forefront of advancing CAR-T immunotherapy, with an eye to reshaping the future of liver cancer treatment.
The quest to discover the unique cell-surface markers of liver cancer proved challenging. In 2021, the team made a major breakthrough with funding from the Hong Kong Research Grants Council’s Area of Excellence Scheme. The grant provided the essential support to conduct a costly RNA sequencing technology that would allow the detection of complex structural variants in the genome.
“Based on this sequencing, we have been able to discover a lot of aberrations in RNA variants and cellular function – and the first-of-its-kind membrane markers of liver cancer cells,” says the professor. “Understanding these aberrations is key to identifying precise markers and developing effective and targeted CAR-T treatments.”
Buoyed by its results, the CUHK team became a pioneer in the field to identify specific biomarkers for liver cancer, and laid the foundation for more research into new therapies and pre-clinical development. Now, with funding from the RAISe+ scheme, Professor Wong is able to take forward the project, “Innovative CAR-T cells for hepatobiliary pancreatic (HPB) cancers”.
CUHK’s extensive patient-derived cell model collection
The key to Professor Wong’s success is the conducive research environment at CUHK, which hosts the most extensive collection of liver cancer organoids and cell lines in the world. “I have spent 20 years building this research and have developed unique models that are bona fide patient derived,” she says. “These models are the essential foundation for the advanced sequencing required to make such discoveries.”
CAR-T cell therapy holds promises in treating solid cancers, but is hindered by challenges: the lack of suitable membrane markers on tumour cells, as well as the risk of “on-target, off-tumour” toxicity in patients. To overcome these limitations, the team not only discovered reliable cell surface markers, but also proposed direct injection of CAR-T cells into the tumour to improve on-target potency.
Genetic engineering solution
There are two ways of administering CAR-T cells into a patient: the systemic way, by introducing CAR-T cells into the patient’s vein and letting them circulate throughout the body, and intratumoral injection straight into the tumour. Professor Wong advises that the first method could still lead to toxicity as patient tolerance and cell behaviour vary significantly, so her team is working to improve the second method. “We shall explore CAR-T cells administration by direct intra-tumoral delivery using EUS and USG-guided percutaneous injection. It will likely overcome the tumour microenvironment effect and improve treatment efficacy.”
The tumour microenvironment often presents a tough barrier for CAR-T cells. It weakens T cell activity and survival by creating an obstacle for T cells to reach cancer cells, reducing their ability to attack tumours effectively. Intratumoral injection is a promising strategy to overcome this hurdle. Under its plans for the RAISe+ fund, the team intends to conduct clinical trials to assess the feasibility and efficacy of this strategy.
The team is also collaborating with local and overseas partners, including Miltenyi Biotec (Germany), the Hong Kong Institute of Biotechnology, which provides facilities compliant with Good Manufacturing Practices, and three supporting hospitals in the cities of Zhongshan, and Guangzhou. “We aim to complete clinical trials in Hong Kong,” says Professor Wong. “We have established a seamless collaboration pipeline that runs directly from our collaborating GMP site on-campus at CUHK to the bedside at Prince of Wales Hospital. It is crucial for ensuring both the quality of T cells and the best possible outcomes for our patients.”
The first phase of clinical trials with 20 patients is set to begin, targeting cancer cells that bear Professor Wong’s first identified marker. Concurrently, the team is going about, as its next objective for research and development, efforts to discover more markers to widen the scope of tumour targets. Since each CAR-T usually recognises only one surface marker, finding new markers would drive the creation of new CAR-T products. A startup company will be launched in due course for commercialisation.
“We envisage the CAR-T cell therapy will become a promising therapeutic regimen for liver cancer, offering patients a new chance of long-term survival,” she says. “We strive to translate this research from the lab to the market, and generate greater societal impact in Hong Kong and beyond.”
By Gillian Cheng
Photos by Steven Yan
All other articles of the second round of our RAISe+ Scheme series can be found here:
- Philip Chiu’s robotic arms project takes digestive cancer operations to new heights
- Ren Wei’s laser sensing innovation aims for global benchmark
- Francis Chan and Siew Ng’s gut research diagnoses and treats autism
- Kwok Ka-wai’s robotic platform provides new level of agility in non-invasive cancer surgery
- Lu Yi-chun’s flow batteries show how we can safely meet our energy needs
