Their findings in mice and companion animals such as cats, published in the Journal of Immunology, are already leading to clinical trials to treat people with various forms of cancer.
Journal of Immunology - Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination
The researchers found that injecting oncolytic viruses (viruses that target cancer cells) intravenously into the spleen boosts immune response faster and higher than traditional vaccine methods. Typically, physicians need to wait weeks or months to administer a booster vaccine, with the down time potentially deadly.
“Normally, you have to wait until the immune response is down to administer the booster vaccine, but this means that, with severe and dangerous diseases, the response would wane,” said pathobiology professor Byram Bridle, lead author of the paper.
“You don’t want to give cancer any time to spread. What injecting the viruses into the spleen does is it allows us to bypass the regulatory mechanism that would limit its effectiveness. When we conducted these tests in animals, we saw high success rates in treatment of cancer.”
He said the findings apply to many types of cancer, including breast cancer, leukemia, prostate cancer and osteosarcoma (bone cancer), and tumours in the brain, liver and skin.
The researchers from Guelph and McMaster University conducted the tests in mice, and in cats brought to the Mona Campbell Centre for Animal Cancer at OVC. Trials on dogs should begin within the next year.
Under traditional treatment options, the tumours grew and mice died. When the researchers started injecting the viruses into the spleen, the tumours disappeared.
“By getting the vaccine to this unique location in the body, we were able to get an unprecedented immune response in minimal time,” said Bridle.
“This is a fundamentally new way to treat cancer that bypasses many common side effects. These therapies are safer and more targeted.”
The findings are already leading to clinical trials for people in Ottawa, Hamilton and Toronto.
Bridle said the study could help researchers in other fields, including those looking to treat virulent diseases such as dengue fever and Ebola.
“My research focuses on cancer, but certainly these findings would be applicable to other diseases. We just need to connect with people in those fields,” he said.
He is optimistic that the human trials will help improve cancer treatment.
“We are living in a world where diseases seem to be growing faster than treatment, so we need to outpace them. Time is of the essence. It’s a race we have to win.”
Effector T cells (TEFF) are a barrier to booster vaccination because they can rapidly kill Ag-bearing APCs before memory T cells are engaged. We report in this study that i.v. delivery of rhabdoviral vectors leads to direct infection of follicular B cells in the spleen, where the earliest evidence of secondary T cell responses was observed. This allows booster immunizations to rapidly expand CD8+ central memory T cells (TCM) during the acute phase of the primary response that is dominated by TEFF. Interestingly, although the ablation of B cells before boosting with rhabdoviral vectors diminishes the expansion of memory T cells, B cells do not present Ags directly. Instead, depletion of CD11c+ dendritic cells abrogates secondary T cell expansion, suggesting that virus-infected follicular B cells may function as an Ag source for local DCs to subsequently capture and present the Ag. Because TCM are located within B cell follicles in the spleen whereas TEFF cannot traffic through follicular regions, Ag production and presentation by follicular APCs represent a unique mechanism to secure engagement of TCM during an ongoing effector response. Our data offer insights into novel strategies for rapid expansion of CD8+ T cells using prime-boost vaccines by targeting privileged sites for Ag presentation.
SOURCES- University of Guelph, McMaster University,