Director, Research Laboratories, BC Cancer Agency’s Trev and Joyce Deeley Research Centre
Adjunct Associate Professor, joint appointment in Biology and Biochemistry/ Microbiology departments
Phone: (250) 519-5705
Research area: immune-based strategies to prevent, detect and treat cancer
The history of cancer research is strewn with potential cancer therapies that look promising in the lab, but don’t work in the real world. One reason that cures remain so elusive is the sheer variety of human cancers. Often a therapy developed against a standardized lab tumour will have limited success when confronted with the individuality of real life tumours.
That is partly why Dr. Brad Nelson’s work at the BC Cancer Agency’s Trev and Joyce Deeley Research Centre is so exciting. Nelson is the Director of the research labs at the centre, where his team is developing an elegant immunological approach to cure a broad range of cancer types. The approach is known as T cell therapy, which is based on the premise that patient’s immune systems can be coaxed to attack and clear a cancer as if it were nothing more than an infection. More specifically, Nelson is isolating T cells (a type of white blood cell that kills abnormal cells in the body) from blood, growing and amplifying these T cells in vitro, then injecting the T cells into mice bearing breast or ovarian cancers. The treatment has had good success in Nelson’s trials with mice, eliminating about 30 per cent of breast cancers with no recurrence, and causing regression of about 75% of advanced ovarian cancers.
One might describe this as T cell doping. The idea is to boost T cells in the patient to the point that the T cells can overcome the tumour. When the therapy worked in Nelson’s mice, it worked dramatically. Five days into a successful treatment, a tumour would be full of T cells; ten days after, the tumour collapsed, leaving only some fibroid scar tissue. Interestingly, T cells lingered in the area after the tumour was gone, and Nelson theorizes they were forming memory T cells against future attacks, explaining the lack of recurring tumours.
Nelson admits he was shocked at the results, explaining that he was not expecting to permanently clear tumours, but was asking the more basic science question of “What tricks will the tumour use to suppress the T cells?”
The seemingly simple idea of T Cell Therapy is not new; it first arose in the 80s. However, the details have proven devilish. Looking back at early attempts made by various researchers, Nelson says it is easy to see now why they didn’t work. The trick is to know how to manipulate immune cells to form the right subset of mature T cells. This requires an in depth knowledge of the chemical communication between immune system cells (a field known as signal transduction), instructing cells to divide, mature and differentiate for an attack; or sit quietly and monitor for the next infection; or to die-off after an infection is cleared. Twenty years ago, cancer researchers simply did not know how to preferentially grow a subset of T cells in vitro. Now they do, thanks to hundreds of researchers worldwide that have been quietly filling in the picture of the incredibly complex web of interactions between immune system cells (including at the CBR, see Dr. Perry Howard and Dr. Robert Ingham).
However there is still more work to do. According to Nelson, one challenge with current protocols is they produce overly mature T cells. Once injected, they only last a couple of weeks – not long enough to be effective. Ideally, T cell therapy would produce T cell precursors, which have a longer life span.
Nelson is tackling this problem by adjusting IL-2 and IL-15 levels in mice receiving T cells (IL-2 and IL-15 are cytokines that stimulate T-cell growth). He has found that if you can increase the amount of these cytokines available for the injected T cells, the T cells expand much more quickly and have a better chance of clearing tumours. The details of how to temporarily adjust the balance of cytokines in human cancer patients is not yet clear.
However, Nelson’s work is encouraging because it worked so well against a variety of tumours. Most cancer researchers induce cancer in model animals by injecting them with a tumour cell line, producing essentially clones of the same tumour. To achieve more variation in his trials, Nelson activated a known breast cancer oncogene, (HER2/neu ) in his mice, which in humans is responsible for 30 per cent of breast cancer cases. Nelson’s team waited for some of the mice to develop breast cancer, mimicking what happens in the real world. The resulting breast cancer tumours looked and acted different from each other (at the molecular level), meaning Nelson’s treatment has a better than average chance of transferring to humans.
Next, Nelson is considering offering the treatment for lymphoma in pet dogs. This program would be part community service – part research. Many pet owners cannot afford cancer therapy for their dogs, and often there isn’t an effective treatment available. There is a good chance Nelson’s T cell therapy could save some of them. Meanwhile, Nelson will be able to try his treatment on a variety of naturally occurring tumours. If it works in dogs, human clinical trials are the next logical step.
A similar success in humans would be a “home run” to use Nelson’s words. Clinical trials in Victoria and Vancouver are expected in three to five years.