For all of our technological progress, one thing that hasn't changed is the toll that disease can take on both individuals and families. Sickness makes no distinction between race, gender, or economic class. But a new class of treatments, known broadly as cell and gene therapies, are increasingly underscoring the divide between individuals of different backgrounds. In particular, the high cost of these therapies, which can often run half a million dollars or more per treatment, is putting a squeeze on the affordability—and hence, accessibility—of these cutting-edge treatments.
The National Research Council of Canada (NRC) has now launched a new program intended to help address these issues—the Challenge Program for Disruptive Technology Solutions for Cell and Gene Therapy aims to design and develop novel cell and gene therapies that will be both affordable and accessible, as well as made in Canada.
"Developing leading-edge therapies against cancer and genetic diseases is all about collaboration," says Lakshmi Krishnan, Director General of the NRC's Human Health Therapeutics Research Centre. "We're working together with our partners in government, as well as across industry and academia, to advance and accelerate the development of technologies for the development of cell and gene therapies for the benefit of Canadians."
Disruptive technology solutions
"Cell and gene therapies are essentially replacement therapies—instead of treating symptoms or managing disease, we can get rid of the underlying problem itself, by correcting faulty genes, replacing defective cells, and repairing damaged tissues," says Program Director Kelley Parato. "These treatments are exquisitely complex, but very effective. Unfortunately, they’re also currently very expensive."
There are a number of ways in which cell and gene therapies can be brought to bear in treating disease. But one of the issues with current cell and gene therapies is that they must be tailored to each individual, which is part of why the cost to patients can often be very high. For example, current CAR-T therapies involve taking a patient's own immune T cells out of the body, re-engineering them in the lab, and then re-injecting them back into the patient.
"In essence, we're training the immune system to fight cancer," says Risini Weeratna, theme lead for program activities in cell therapy. "Of course, this has to be done one person at a time, using the patient's own cells as a starting point."
The development of a 'universal' donor cell would be a significant first step in helping to reduce the costs of cell and gene therapies. Using induced pluripotent stem cells (iPSCs), NRC researchers are aiming to create cells that could be used as a starting point for the development of therapies to target diseases and genetic disorders. These cells would be 'universal' in the sense that—instead of taking them from individual patients—they'd be available for 'off-the-shelf' use. In other words, they'd begin in a lab instead of the individual patient, and be engineered to fight a specific cancer or genetic disorder, while also avoiding rejection by the patient's natural immune system.
"We're developing new tools and using artificial intelligence (AI)-assisted design to engineer iPSCs with enhanced "stealth" properties," says Anna Jezierski, Project Lead for the program's Precision Engineering thrust. "These unique cells will help scientists create a suite of off-the-shelf cell therapies tailored to fight cancer and degenerative diseases. We want to move from a one-to-one to a one-to-many treatment approach—allowing for a significant reduction in cost, thereby enabling improved accessibility and affordability."
Over the longer term, researchers are aiming to develop biodevice technologies that will allow cell and gene therapies to be delivered in a distributed manner via microfluidic-based technology.
"Imagine a portable instrument—say, a small box—that contains the capacity for the manufacture of a cell therapy, supported via an automated system with embedded and continuous analytics and quality control, which could produce a targeted cell therapy for a patient on the spot," says Lidija Malic, researcher for the NRC's Medical Devices Research Centre and project lead for the program's biodevices project. "It may sound like science fiction, but this type of technology may well be in view within the next few years."
A test case for success
To get a sense of the scope of the problem, one need look no further than Glybera—the world's first approved gene therapy, which was approved in Europe at a price tag of $1 million per treatment. Glybera was intended to treat a genetic condition called lipoprotein lipase deficiency (LPLD), but only one dose was sold at full price in Europe before the drug was pulled off the market.
"In a sense, it's our way of bringing the technology home," says Danica Stanimirovic, who is leading the project. "The science behind this gene therapy aimed at treating LPLD was developed here in Canada, and the resulting treatment was first validated here in Canada. But it was never made available to Canadian patients. That's something that we're aiming to fix."
Collaborating for health
In the end, what unites these women is their shared commitment to improving health outcomes for all Canadians.
"The reality is that developing new health therapies takes time," underscores Krishnan. "Our aim is to accelerate development wherever possible, in order to encourage innovation, while also ensuring safety and efficacy. In the lab, we deal with data and analysis. But outside the lab, the people who need treatments may one day be a brother or a sister, a parent or a loved one. We always try to keep in mind the human element of what we do. That perspective helps us to work that much harder and effectively towards finding real solutions."