PharmSci research advances understanding of immunotherapy

New details of immune system molecules could help diagnose and treat inflammatory conditions

Immunotherapy is a promising treatment strategy for many conditions where an imbalanced immune system response contributes to a patient’s symptoms. Jean Gariépy, Professor (Status) at the Leslie Dan Faculty of Pharmacy and senior scientist at Sunnybrook Health Sciences Centre, leads a research program that focuses on immunotherapy and designing antibodies and biospecific molecules that can be used to diagnose and treat conditions including cancer, inflammatory bowel disease (IBD) and psoriasis.

“Immunotherapy treatments are focused on blocking the action of inflammatory cytokines that are produced by activated immune cells,” says Gariépy. “Blocking the action of specific cytokines with antibodies or protein therapeutics has led to life-altering therapeutics for rheumatoid arthritis, psoriasis, colitis and cancer.” 

In a recent publication, Gariépy and his team developed molecules aimed at a newly discovered immune checkpoint regulator called VISTA. This immune system regulator is typically found on a type of white blood cell called myeloid cells and mainly functions to reduce inflammatory responses. In conditions where the immune system is overactive, such as psoriasis, enhancing VISTA activity and dampening the inflammatory response could be a useful approach.

The research team developed monoclonal antibodies and tested whether they could activate VISTA activity in cell cultures and models of psoriasis. Several of the monoclonal antibodies they developed generated promising results and will be explored in further work.

“In the case of this research, antibodies that activate VISTA may prove useful in treating inflammatory or auto-immune diseases,” says Gariépy.

“A lot of research is also ongoing that explores the use of agents that can block the action of VISTA to restore anti-tumour immune responses, as they could be used with FDA-approved immune checkpoint inhibitors in cancer therapy.”

Biospecific molecules offer potential for highly targeted immunotherapy

In another line of work, Gariépy and his team have been developing and delivering biospecifics – proteins that are designed to locate and bind to a specific target – to diagnose and treat a variety of conditions, including IBD.

Current IBD treatments suppress the immune system broadly and can have harmful side effects. Gariépy’s team is working to develop highly targeted molecules that can treat IBD without broad immune system suppression.

In March, Gariépy received a five-year, $868,000 grant from CIHR to develop new biospecific molecules with the potential to treat IBD at lower doses with fewer side effects. They will then test these molecules in models that display gut inflammation similar to IBD. The grant application was ranked first in its panel.

The research team has previously developed and tested biospecifics that targeted markers of breast cancer and could be used for diagnosis. But the new grant provides opportunities to test biospecific molecules as therapeutics.

“Our goal is to develop a simple, rapid assembly strategy of anti-inflammatory biologics to guide them to the gut to treat IBD patients with fewer side effects,” he says.