The fight to stay one step ahead of cancer cells
Dr Gloria Lin (Croucher Fellowship 2012) is working to find new answers to a complex disease that affects many people all over the world and still eludes scientists: cancer.
After receiving her PhD from the University of Toronto in 2011, Lin began a postdoctoral fellowship at the lab of Dr Tak Mak at the Ontario Cancer Institute. Lin now works as an Associate Director in Translation Research for Trillium Therapeutics in Canada, looking to develop new cancer therapies.
“Treating cancer is not simple, [the cells] can be killed easily, but oftentimes they come back and become more aggressive. That’s why there are so many drugs out there and cancer cells can become resistant to most of them,” Lin observed.
Since starting at Trillium, Lin has been involved in preclinical studies, animal models and clinical trials. Developing a new therapy is a long process and requires rigorous testing in animals to determine preliminary toxicity and proof of concept before any trials can begin in human subjects.
“Once a drug enters clinical development, there are three major phases: phase one is for safety; phase two is for efficacy; and phase three is to test in bigger and broader populations,” she explained.
Lin’s doctoral studies were focused on the co-stimulation of T cells, which are a type of lymphocyte, as part of the body’s immune response. “My PhD work was to understand how we can trigger T cell killing activity against infections and tumours. These studies have been instrumental to my current work to develop immune-modulating therapies against cancers,” she said.
Fighting cancer cells requires intensive and varied treatment. Often, multiple drugs are needed to counteract tumours. “Cancer cells will change to adapt, so for a lot of drugs in the cancer field, it’s hard to do monotherapy,” she said.
Lin’s work focuses on marshalling the body’s natural defences to fight cancer cells. Our immune systems release antibodies, or white blood cells, to protect our bodies from viruses and bacteria. The real challenge is making our bodies recognise cancer cells as a threat.
“CD47 is a molecule found on most cells. However, it's upregulated on a lot of cancer cells,” Lin said. This overexpression of CD47 on the surface of cancer cells is to trick the patients’ immune systems into thinking that the cancerous growths are normal healthy tissue.
“CD47 sends a ‘do not eat me’ signal to the host’s immune system,” she said. “When cancer cells upregulate CD47, it binds to the SIRPa receptor on macrophages and that stops the macrophages from ingesting the tumour cells.”
Drugs that target CD47 would allow the immune system to fight cancers. “At Trillium, our drug is an IgG fusion protein decoy receptor [that] binds and blocks CD47, and it triggers macrophages to eat the cancerous tumour cells through a mechanism called antibody-dependent cellular phagocytosis,” Lin said.
Once a drug enters clinical development, there are three major phases: phase one is for safety; phase two is for efficacy; and phase three is to test in bigger and broader populations.
Lin documents and evaluates the outcomes of these treatments in animals and in patients. “I design the animal models in the pre-clinical development, and I manage the analysis of tumour biopsy samples and blood samples from patients in clinical studies,” she noted.
To better understand how the patient’s body will interact with potential therapies, Lin looks at biomarkers from these samples. “We can find specific markers that patients have before treatment and these markers can predict whether the drug works or not.”
It is still early days for this type of treatment, but Lin is optimistic. “I think eventually we will cure cancer but the approach will likely be a combination therapy,” she said. “Given the complicated biology of different cancer types, having multiple drugs and multiple approaches is necessary to increase the chance of success in producing a cure.”
Looking ahead, she expects personalised therapies will become de rigueur. “Treatment on an individual basis rather than treating all patients with the same strategy will make more sense, since patients with the same type of cancer can have very different biology and responses to treatment,” Lin explained.
As Lin and her team continue to develop a therapy that modulates our immune system to fight back, we are one step closer to finding a cure to a disease that has long afflicted people of all ages.
Gloria Hoi Ying Lin completed her Honours Bachelor of Science in Immunology at the University of Toronto with high distinction in 2006. She then joined Dr Tania H Watts' laboratory in the Department of Immunology at the University of Toronto, as a doctoral student and received her Doctor of Philosophy degree in 2011. During Lin’s graduate study, she developed a great interest in understanding how costimulatory molecules fine tune immune response. She went on to become a post-doctoral fellow in Dr Tak Mak's laboratory at the Ontario Cancer Institute. She received her Croucher Fellowship Award in 2012. She is now a research scientist at Trillium Therapeutics Inc, Toronto, Canada.
To view Gloria Lin’s Croucher profile, please click here.