Researchers in the Department of Microbiology and Immunology have teamed up with scientists at Robarts Research Institute to bring their research on cancer immunotherapy to the next level. Their work is showing how the bacteria primarily responsible for causing strep throat can be used to fight colon cancer. By re-engineering a streptoccocal bacterial toxin to attach itself to tumour cells, they are forcing human immune cells to recognize and attack the cancer.
Kelcey Patterson, a PhD Candidate and lead author on a study published in the April edition of PLOS One, showed that the re-engineered bacterial toxin could significantly reduce the size of human colon cancer tumours in mice, with a drastic reduction in the instances of metastasis. The work was funded by the Canadian Institutes of Health Research and directed by John McCormick, PhD, associate professor in the Department of Microbiology and Immunology with collaborators Mansour Haeryfar, Phd, in Microbiology and Immunology, and David Hess, PhD, a scientist at Robarts Research Institute.
This isn’t the first time that researchers have used engineered bacterial toxins to fight cancer in pre-clinical testing, but McCormick says their research provides move evidence that this may work in humans. “Other groups have done similar experiments, but this really is the next generation super-antigen immunotoxin,” McCormick said.
The challenge of this experiment was finding a mouse model that could replicate what happens in the human body. A normal mouse’s immune response would automatically destroy all the human cells that are required to target the tumour.
This is where Robarts scientist, David Hess steps in. Hess, a stem cell biologist, doesn’t usually study cancer, but was able to use his knowledge and expertise of immune-deficient animal models to help push the research forward.
By using mouse models that are completely stripped of their immune systems, they were able to create a “humanized mouse” – one that would not only grow human cancer cells, but would also support human immune system function after the transplantation of blood cells.
“We normally use this mouse to study the regenerative function of human stem cells. For example if we transplant human bone marrow stem cells into this mouse they will form a completely human blood system," Hess said. “It is the only way to do this kind of preclinical testing before going into actual clinical trials in humans.”
It’s collaborations like these that are fuelling some of the most groundbreaking work into the study of human disease. Hess and McCormick recently received a grant from the Cancer Research Society to continue exploring how different bacterial toxins and antibodies might be used in combinations to fight other types of cancer.
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