Cell therapies are integral to regenerative medicine: a swiftly advancing sector bearing the long-standing promise of revolutionizing health care as we know it. Unlike drugs that merely relieve symptoms, cell-based treatments possess curative potential by delivering a dynamic, living product to both counteract the underlying disease cause and promote regeneration. Healthy cells derived from either the patient or a compatible donor, once transplanted, can retain their ability to divide, migrate, differentiate and produce biological factors – mechanisms that have been shown to create lasting, transformative effects in an ever-widening spectrum of clinical conditions.
Regenerative medicine has been hailed a new era in medicine, with 2017’s US Food and Drug Administration’s (FDA) approval of the CAR-T immunotherapeutics Kymriah (Novartis) and Yescarta (KITE Pharma) creating a new wave of excitement and activity in the industry. This has been elevated by a steady stream of positive clinical trial data from emerging cell therapies, for conditions from cancer and diabetes to neurodegenerative disorders.
Regenerative medicine has been hailed a new era in medicine, with 2017’s US Food and Drug Administration’s (FDA) approval of the CAR-T immunotherapeutics Kymriah (Novartis) and Yescarta (KITE Pharma) creating a new wave of excitement and activity in the industry.
Regulatory bodies are responding to the quickly expanding market with appropriate measures to boost cell therapy product development for an equally growing patient base. The 21st Century Cures Act, signed in 2016, provides cell therapies with a special designation through the FDA’s Regenerative Medicine Advanced Therapy pathway. Humacyte and Vericel are among the first to place their products on this expedited approval pathway, with many others expected to follow suit.
The evolution of effective and accessible therapies for life-threatening diseases is further supported by a steep rise in investments being pumped into cell therapy product pipelines. Michael May, president and chief executive officer of the Centre for Commercialization of Regenerative Medicine (CCRM) in Toronto, sees a swell of investor funding in Canadian cell therapy enterprises as being a positive indicator of growth on the national front.
“Companies such as BlueRock Therapeutics and AVROBIO are drawing capital from global investors and putting Canadian biotech on the map. There is a goldmine of opportunities for Canada to become a world leader in cell therapy manufacturing.”
Toronto-based BlueRock Therapeutics, founded in 2016, pocketed a massive US$225-million investment from Versant Ventures and Bayer AG, propelling their regenerative science straight into the clinical trial phase. Blue Rock’s product pipeline includes therapies for various conditions within the neurodegenerative and cardiovascular disease space. This is a prime example of Canada’s ability to attract investor dollars by leveraging world-class scientific research, access to commercialization consortiums such as CCRM and its capacity for manufacturing biological products for a global market.
Despite recent successes and high hopes, however, the scarcity of cell therapies presently available to patients points to its relative infancy in the commercialization cycle. Manufacturing human cells as deliverable products represent a major hurdle standing in the way of a smooth “bench to bedside” transition.
Another cell therapy rising star, RepliCel Life Sciences, is harnessing the healing properties of hair follicles to address unmet medical needs in acute, chronic and genetic conditions. RepliCel’s product pipeline features a diverse portfolio spanning tendinopathies, pattern baldness, skin damage and dermal injector medical devices. Lee Buckler, president, CEO and director of RepliCel describes highlights from his journey in the cell therapy sector: “The most exciting breakthrough during my time with the team has been transitioning from a pre-clinical to a clinical stage company.” RepliCel, with headquarters in Vancouver, attributes its success to fruitful industry and academic collaborations: partnerships with Japan’s Shiseido and research stemming from the University of British Columbia.
Buckler’s advice to other cell therapy entrepreneurs? “Don’t try to do this by yourself. Align yourself with sophisticated partners and capital out of the gate. Also, do not assume great technology results in great products – never lose focus on the eventual product.” Speaking on pathways specific to cell therapy development, he adds, “Ongoing basic research will continue to inform the process, the product, the assays and the regulatory strategy until much later in the development cycle than other biologics.”
Despite recent successes and high hopes, however, the scarcity of cell therapies presently available to patients points to its relative infancy in the commercialization cycle. Manufacturing human cells as deliverable products represents a major hurdle standing in the way of a smooth “bench to bedside” transition. Scale up and scale out of cells while assuring their purity, safety, potency and commercial viability remains a challenge, even for well-established manufacturers.
For some cell therapy applications, there is the possibility for generating cell banks of allogeneic cells from healthy donors. These “off-the-shelf” cell therapies are more cost-efficient, can be mass produced and allow for automated systems to be integrated into production lines. However, creating personalized immunotherapies, such as CAR-T, that harness the patient’s own immune system to fight disease, involve costly, labour-intensive and time-consuming procedures. In both cases, closed cell expansion and modification systems that reduce the risk of operator variability and contamination are ideal for preserving the quality of the final product.
For some cell therapy applications, there is the possibility for generating cell banks of allogeneic cells from healthy donors. These “off-the-shelf” cell therapies are more cost-efficient, can be mass produced and allow for automated systems to be integrated into production lines.
Canadian engineering innovation just may provide solutions to these remaining obstacles. Ontario’s Octane Biotech, for example, is in the business of developing next-generation bioreactors, bioprocesses and biomaterials that are set to transform cell therapy manufacturing. Octane’s Cocoon™ bioreactor offers customizable automation from donor to the eventual cell product, thus doubling efficiency and slashing production costs.
Besides cultivating cells for therapeutic use, manufacturing also involves an intricate genetic manipulation step prior to reintroduction into the patient. As CCRM’s CEO Michael May explains, “There is a rapid convergence of cell and gene therapy happening in the field. Most cell-based products in the future will be genetically modified in some way or other. The scale-up of existing genetic modification tools like CRISPR-Cas9 and non-viral transfection methods also represent a barrier to full industrialization of these revolutionary products.”
Vancouver-based Precision NanoSystems has developed breakthrough microfluidics platforms to streamline and enhance the delivery of nucleic acids to cells via the use of nanoparticles. This technology has immense potential in gene and cell therapy manufacturing applications. Using nanoparticle carriers with a plasmid, mRNA or siRNA cargo eliminates the safety hazards associated with the use of currently-used viral vectors like lentiviruses, while simultaneously minimizing the impact on sensitive cells to maximize therapeutic outputs.
Though limitations in industrial scale cell therapy production still linger, the future looks bright for Canadian enterprises that are actively dedicating themselves to overcoming such challenges. “There is a lot of exciting activity happening in Toronto, Vancouver, Ottawa and Montreal right now,” May explains. “We should be coordinating our efforts across the country and collaborating with global partners to make cell therapies more accessible to patients.” With the monumental burden of serious diseases on health care systems set to skyrocket in the future, the time is now for Canada to drive cell therapies as a valuable complement to conventional medical approaches.
Tara Fernandez is a Vancouver-based Cell Biologist and science communicator. Her research focuses on new ways to treat cells on the nanoscale.