Dr. Tak Mak may be one of Canada’s most prominent researchers, but he’s certainly not resting on his laurels. Mak recently completed a three-year study, funded by the Ontario Institute for Cancer Research (OICR), that could result in a more benign therapy to treat Hodgkin’s lymphoma.

Currently, Hodgkin’s lymphoma is diagnosed in about 900 Canadians every year, most of whom are between the ages of 15 and 35. About 80 per cent of patients survive, but current treatments – including radiation and chemotherapy – have a long list of side effects that include a high rate of sterility and the development of other secondary tumours. Around 15 per cent of patients currently treated and “cured” of Hodgkin’s lymphoma develop a secondary tumour within their lifetime, sometimes as a result of the treatment itself.

“What we’re talking about here is a disease that hits young men and women that is, by and large, curable. But we’re still losing some of them, and we lose more of them down the road,” Mak says.

In 1999, Mak’s team made a major breakthrough in Hodgkin’s lymphoma research, discovering that the disease’s tumour cells proliferate uncontrollably due to a growth factor present in the human body called interleukin-13 (IL-13). Further, they found that depriving Hodgkin’s lymphoma tumour cells of IL-13 causes these cancer cells to stop growing and, in some cases, die off completely. 

Mak has spent the past three years using animal models to develop antibodies to block IL-13 production. The team has identified several mouse antibodies that can inhibit IL-13 production. By inserting these antibodies into mice, IL-13 production gradually ceases, and the tumour itself is starved and dies. “We now have very good antibodies against IL-13 and they work very well at sequestering and removing tumour cells,” Mak confirms.

One of the most promising aspects of this therapy is that it may treat the disease without side effects. The antibodies could be injected into the body using a needle, and could significantly reduce the amount of chemotherapy and radiation required – if not supplant these therapies completely.

“This is a benign treatment,” Mak says. “We don’t need IL-13 in our bodies so there should be zero side effects. If this works, it will forever be a better treatment than chemotherapy and radiation.”

IL-13 is found naturally in the human body, used by the immune system to fight parasites. Using an injection of antibodies to temporarily reduce the amount of IL-13 in the body thus has little effect on its day-to-day functions. Since the developed world has very few parasites for patients to worry about, and the developing world has very few cases of Hodgkin’s lymphoma, treatment could be widespread with little interruption to a patient’s lifestyle.
 
“This is an excellent project that has the potential to radically increase the ability of people with Hodgkin’s lymphoma to live a normal life while undergoing treatment,” says Dr. Tom Hudson, President and Scientific Director of OICR. “We are pleased that we could assist Dr. Mak in this phase of his work on this extremely promising therapy.”

However, Mak makes clear that while the IL-13 antibody used in his research has been successful in animals, it remains a mouse antibody. If it were injected into a human, the human immune system would make an antibody against it – not knowing it was trying to help – and remove it from the body. A new phase of research involving the creation of a human form of this antibody is necessary to move the project forward for human use.

Mak remains positive about the therapy’s potential. He is preparing the project’s next phase and he remains hopeful a therapy using IL-13 antibodies will be available within the next three years.

After that, he hopes that this therapy can one day go on to treat other types of cancer. “Once we have the proof of principle for Hodgkin’s lymphoma,” he says, “there may be other cancers that can benefit from this treatment.”

Mak’s work on Hodgkin’s lymphoma is one small part of his contribution to science in Canada (go to story on Mak’s career). Mak is most widely known for discovering and characterizing the human T cell receptor gene in 1984, a key part of the human immune system. He is currently the Director of the Advanced Medical Discovery Institute, the Director of the Campbell Family Institute for Breast Cancer Research and a Senior Scientist in the Division of Stem Cell and Developmental Biology at the Advanced Medical Discovery Institute/Ontario Cancer Institute.

Above: Dr. Tak Mak in his lab with researcher Annick You-Ten.