TFRI-funded researchers from the Canadian Oncolytic Virus Consortium (COVCo) have found a way to improve the efficacy of therapeutic cancer vaccines, according to a new paper published in the Journal for Immunotherapy of Cancer (July 2020).
Led by virologist Dr. Brian Lichty (McMaster University), the team found that administering a single low dose of the chemotherapy drug cyclophosphamide (CTX), a day before vaccination, provided a one-two punch that increased the immune system’s ability to fight cancer.
“This combination transformed the therapy from one that merely extended survival to one with curative potential,” said Dr. Byram Bridle (University of Guelph), a member of the COVCo team and one of the paper’s authors.
Their finding was made in a pre-clinical mouse model that simulated lung metastases from melanoma.
The promise of cancer vaccines
Oncolytic vaccines work by introducing small amounts of harmless viruses into the body of patients. These viruses stimulate the immune system, helping it fight cancer cells.
Although these vaccines have long been seen as promising therapies, researchers have found that when administered on their own, cancer vaccines fail to overcome certain roadblocks created by the immune system, such as those presented by regulatory T-cells. These cells prevent the vaccines from fully stimulating the immune system, making the vaccines ineffective.
By using a known immunosuppressant drug like CTX, the team was able to selectively deplete regulatory T-cells, allowing the cancer vaccines to fully activate the immune system against cancer cells. When tested in mice, administering CTX a day before injecting the vaccine resulted in complete remission in the majority of the animals.
“It would seem counterintuitive to use a known immunosuppressant drug to potentiate a cancer immunotherapy, yet we found that this combination enhanced tumour-specific immune responses by selectively depleting immunosuppressive regulatory T-cells,” explained Dr. Bridle. “It’s really a novel combination therapy that holds potential to transform how patients with cancers are treated in the future.”
Enhanced immunotherapeutic profile of oncolytic virus-based cancer vaccination using cyclophosphamide preconditioning
Jonathan G Pol, Matthew J Atherton, Kyle B Stephenson, Byram W Bridle, Samuel T Workenhe, Natasha Kazdhan, AJ Robert McGray, Yonghong Wan, Guido Kroemer, Brian D Lichty
This study was partly funded by the Terry Fox New Frontiers Program Project Grant to the Canadian Oncolytic Virus Consortium (COVCo)