TAKING IMMUNOTHERAPY TO THE NEXT LEVEL
Thirty percent of all open clinical trials at The Princess Margaret use immunotherapy. That includes testing new drugs alone or in combination with other drugs to give patients their best outcome.
Pembrolizumab is an immune checkpoint inhibitor drug which lifts the “brake” on tumour fighting T-cells to enable them to attack the enemy in the battleground or tumour microenvironment.
That drug is currently part of a flagship clinical trial at The Princess Margaret called INSPIRE (Investigator-initiated Phase II Study of Pembrolizumab Immunological Response Evaluation). The study was launched in March 2016. The objective is to evaluate the changes in the genetic signatures and immune landscapes in patients with various advanced solid tumours when treated with pembrolizumab.
Since its initiation, more than 100 patients with head and neck, breast, ovarian, melanoma and other advanced solid tumours were enrolled. Even though analysis of the results from INSPIRE is still in the early stages and ongoing, principal investigator Dr. Lillian Siu says the findings could be an important step in moving the research in immunotherapy forward.
“If we have some hints on which patients respond better and those who do not, then we can further test these hints in additional studies. I think that’s very important in personalizing immunotherapy.”
Because some of these drugs also have toxicity risks that could be severe in a small percentage of patients, understanding how to use these drugs more effectively is crucial.
There is evidence that the bacteria and microorganisms in our bodies, especially those that grow and thrive in our gut, could have something to do with how our bodies respond to various cancer therapies, including immunotherapy.
Researchers are currently working with everyone from microbiologists to infectious disease specialists and using technology such as bioinformatics, data science and artificial intelligence to analyze the complex data.
“We’re hoping the next step is to create a microbiome program, as well as a data science and an artificial intelligence program that are closely linked to help us understand this new information,” says Dr. Lillian Siu.
A new trial in head and neck cancer has already begun. Saliva, throat swabs and stool samples are being collected from patients undergoing chemotherapy and radiation to see how the bacteria profiles in their gut and in the throat correlate with one another and with response to treatment. Dr. Siu says the next step is to attempt to change the bacterial composition in a patient’s gut. This could be done by testing through clinical trials the addition of oral probiotics (some of which contain favorable bacterial strains), or one day, transplanting fecal microbiome from one patient’s gut to another.
“It sounds far-fetched, but it’s actually not. People have already started to think about that and we have researchers at The Princess Margaret who are experts in this area. We’re collaborating with them on these fronts.”
WHAT ARE CAR T-CELLS?
WILL THEY CHANGE THE WAY CANCER IS TREATED?
There has been a lot of buzz in the scientific community about CAR T-cells being a promising new form of immunotherapy, that could revolutionize the way certain types of cancers are treated.
Chimeric antigen receptor, or CAR T-cell therapy, is a form of adoptive T-cell treatment that is already demonstrating success in some forms of adult lymphomas and childhood leukemias.
“This is going to be an opportunity for us to potentially change a standard of care,” says Dr. John Kuruvilla, a hematologist at Princess Margaret Cancer Centre.
Engineering cells for transplants in blood-based cancers is not new but the technology behind CAR T-cells is. “It is a more targeted way to treat blood cancers as well as solid tumours,” says Kuruvilla.
“These CAR T-cell treatments are going to be compared against traditional stem cell transplant therapies and there will be a huge opportunity in Canada for us to lead those studies,” he says.
While CAR T-cell therapy is currently only approved in the United States for certain blood cancers, The Princess Margaret is developing more effective and potentially safer versions of CAR T-cells.
Senior Scientist Dr. Naoto Hirano was featured in the prestigious journal Nature Medicine in early 2018 for his team’s work engineering a CAR molecule that has the potential to enhance the effectiveness of existing immune therapies.
Optimizing these CAR molecules could make CAR T-cell therapies more effective. It would enhance therapies for lymphoma targeting the tumours and the tumour microenvironment where resistance to treatments can develop.