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Priming the body’s defence system to seek and destroy cancer

Immunotherapy shows much promise in the fight against cancer. Associate Professor Toh Han Chong, Senior Consultant and Deputy Director, National Cancer Centre, talks about his 20-year research journey in this field and the promise of this new form of treatment for cancer. 

How did you get involved in this research?
When I started doing immunotherapy research in the late 1990s, it was an unfashionable field which many thought held little promise and little clinical relevance to improve the lives of cancer patients. Several people even warned me that it could harm my career as an academic oncologist! But I’ve always been fascinated by the immune system, and the theory of using it to fight cancer made scientific sense to me if only we could understand it better. Thankfully, I followed my hunch and it’s very satisfying to see the progress this field has made over the past two decades and especially in the last few years.

For years, researchers were able to show that immunotherapy could treat cancer in mice and other animal models. But the international scientific community only took notice from 2011, when researchers in the United States announced the first successful treatments that could extend survival and even effect cures in humans. Among these was the case of Emily Whitehead, a six year old girl who was dying from her relapsed acute lymphoblastic leukaemia after receiving all possible treatments. Her parents enrolled her in a Phase I immunotherapy clinical trial at Children’s Hospital of Philadelphia, USA, in a desperate attempt to save her life. The course of treatment, which used her own T-cells engineered to attack a specific cancer surface protein, was rough but the results were staggering. All traces of cancer disappeared within days and Emily has been cancer-free since.

Since then, research and clinical trials in cancer immunotherapy has boomed and it is now seen as the next major advancement in cancer treatment.  

What is immunotherapy?
The immune system is designed to defend the body against infections and other diseases. But cancer cells are masters of disguise and deception so instead of attacking these malignant cells, some parts of the immune system can actually help in this evasion and protect them from an immune attack! 

Immunotherapy stimulates and enhances the body’s immune system to fight cancer. There are several different types that are often used either as single treatments or in combination. They include:
  • Cancer vaccines which stimulate the immune system  to attack cancerous cells 
  • Monoclonal Antibody Therapy - antibodies, similar to those produced by the body, are given to target specific proteins on cancer cells or unleash the immune system close to the cancer to attack the cancer cells.
  • CAR-T Immunotherapy (a form of Adoptive T-cell Therapy) - a patient’s T-cells are genetically modified so they recognise and hone in to kill cancer cells. These T-cells are carefully manufactured and processed in the laboratory then returned to the patient where they seek out and kill cancer cells.
  • Other forms of cancer immunotherapy include viruses that can cleverly reproduce in cancer cells and not normal cells (oncolytic viruses), other forms of T cell therapies that can deliberately attack cancer and substances called cytokines that can further stimulate the body’s immune system to fight cancer.

How effective is immunotherapy and will it replace chemotherapy one day? 
Immunotherapy has been shown to be especially effective in treating melanoma (skin cancer), lymphoma and leukaemia. In some cases like Emily’s, patients who had only months to live have been cured by CAR-T Immunotherapy and have been cancer-free since. These patients are fondly referred to as ‘super-survivors’. Antibody therapy, which unleashes the body’s T-cells to fight cancer, has also shown to yield impressive responses in many types of cancers, with ‘super-survivors’ for cancers such as melanoma for up to ten years and beyond. 

Although immunotherapy can potentially replace chemotherapy for some cancers, it’s not a universal cure-all magic bullet.  It is still in its infancy as a cancer treatment, but has huge potential to cure more types of cancers. Ultimately, I hope that immunotherapy will enable more cancer patients to regain their health, enjoy good quality lives by keeping the disease under control for many years.

What areas of immunotherapy are you working on?
My team at NCCS focuses on developing immunotherapy for cancers of the nose (nasopharyngeal cancer), colon, breast, ovary and liver.  These are priority areas - bowel cancer is the most common cancer in Singapore and nasopharyngeal cancer is particularly common in Southeast and East Asians. At the same time, we are investigating why some patients respond so positively to immunotherapy, while others are resistant to this form of treatment.

Working with a local biotech company, we are currently conducting the world’s first Phase 3 T-cell immunotherapy clinical trial for all types of cancer. We hope to recruit over 300 patients with advanced, terminal nasopharyngeal cancer to participate in this trial in a quest to potentially improve survival rates and quality of life in these patients.