Professor Leung Wing Hang has made it his life’s mission to find better ways to treat childhood cancers. The renowned haematologist-oncologist and researcher joined KK Women’s and Children’s Hospital (KKH) earlier this year and was conferred the Tan Cheng Lim – CCF Professorship in Paediatric Oncology. Prof Leung shares what drives his research and his plans to transform paediatric cancer care in Singapore.
What inspired you to specialise in childhood cancers?When I was a house officer in Hong Kong 30 years ago, I took care of a teenager who had been admitted to an adult ward with acute megakaryoblastic leukaemia – this is a form of leukaemia from platelet-producing cells. He suffered greatly from complications caused by chemotherapy and ended up dying from persistent leukaemia. He inspired me to find a better way to cure cancer without the serious side-effects of chemotherapy, so I went to Johns Hopkins University to pursue a PhD focusing on cellular therapy.
I went on to work at St Jude Children’s Research Hospital (St Jude), USA, for nearly 20 years, where I treated children with leukaemia and lymphoma and continued my research on cellular therapy, concentrating on ways to improve bone marrow transplants and immunotherapy. About three years ago, I started working part-time in Singapore and introduced some of these developments.
How do childhood and adult cancers differ?Adult cancers are usually caused by viruses, exposure to carcinogens or the ageing process, which cause multiple genetic mutations over time and eventually lead to cancer. But in children, cancer is nearly always caused by fewer genetic mutations, some of these they are born with. Therefore the type, spread and treatment of cancers differ between children and adults.
KKH sees about 100 to 120 new cases of childhood cancer a year which make up about 70% of the cases diagnosed in Singapore. Of these, leukaemia and lymphoma make up about half while the rest are tumours.
Although survival rates in young cancer patients have improved greatly over the years, survivors often face the risk of long term side-effects to their vital organs and brain development caused by chemotherapy and radiotherapy. That’s why it is so important to develop better ways to treat cancer in children.
Tell us about cellular therapy and your research.Cellular therapy uses human cells instead of drugs or radiotherapy to treat the body. My research in this field focuses on three fundamental questions:
• How to do a bone marrow transplant (BMT) when a patient does not have a matched donor?• How to ‘tweak’ the body’s natural killer cells so they will attack cancer?• How to improve antibody treatments for cancer?
Previously, patients needed to have a matched donor in order to receive a BMT, and finding a match often proved challenging. My research at Johns Hopkins and St Jude addressed this problem, and using novel graft engineering techniques, we can now do mismatched transplants successfully without the usual complications such as rejection or serious infection. I brought these technologies to Singapore when I was working here part-time, and so far, more than 20 children and adults here have received these unmatched BMTs.
Natural killer cells are a type of white blood cell that naturally controls infections. We now have a better understanding of how these cells work and we are able to select the best donor to kill cancer cells.
Many antibodies can also be used to treat cancer, however they need repeated injections and many cancers ultimately recur. By using synthetic biology, we can now incorporate fragments of antibodies into natural killer cells or other immune cells to kill cancer precisely. The cells attack the tumour in a way similar to how childhood vaccines protect the body from infections. One infusion in the clinic may be enough to treat the cancer, and some childhood cancers appear to be particularly susceptible to this type of treatment.
So far, leukaemia and lymphoma have been treated successfully with this combined immunotherapy. Now the research focus is expanding to include effective treatments for paediatric solid tumours in the brain and neuroblastomas, which are very aggressive nerve tumours that often prove fatal.
Why did you decide to leave the USA and join KKH full-time?
"Every child is precious no matter where they live. I want to help bring this biotechnology to Singapore and Asia, because every child deserves the chance to be cured of cancer. " - Professor Leung Wing Hang
I believe SingHealth and Singapore are well-placed to drive this technology both here and in the region as it has the right supportive environment and the necessary biomedical talent for such research to succeed.
What are your main areas of work in Singapore?I am leading the Paediatric Cellular and Immunotherapy Programme which is focused on four key areas:
• Setting up a Chimeric Antigen Receptor T Cell (CAR-T) and Natural Killer Cell Programme for Singapore in collaboration with the Health Sciences Authority• Building a Transplant and Cell Therapy Programme to provide transplant care which was not previously available• Conducting research in transplants and immunotherapy• Nurturing a new generation of physician-scientists
What challenges are you facing?I’m starting a cell therapy programme from scratch, so I need everything – from a facility to equipment and staff. Every immunotherapy product is specifically tailored to each patient’s unique needs. Therefore, each product must be created in an individual clean room with its own air handling unit to prevent contamination. This requires a lot of physical space which is always a challenge in Singapore!
The cost of the infrastructure, bringing in equipment, reagents and training staff to establish the centre runs into millions of dollars, so financial resources are also a real challenge. But this is an investment that can be used to develop immunotherapy products for both children and adults who are suffering from cancer, resulting in more lives saved without the distressing side-effects of traditional cancer treatments.
How will this Professorship further your research?There is still much work to be done to increase our understanding of immunotherapy, improve outcomes and bring down the cost to make it more affordable. This Professorship, which was made possible by the generous support of Children’s Cancer Foundation (CCF), is co-named after Professor Tan Cheng Lim, one of Singapore’s pioneers in paediatric oncology. I’m honoured to be conferred this Professorship, which will enable me to delve deeper into these areas of research and invest my time in training the next generation of physician-scientists in leading-edge cellular biotechnologies so that more can be done to save precious young lives.
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