Dr. Rohin Iyer is currently a Development Manager at GE Healthcare / CCRM. He did his PhD in Biomedical Engineering at the University of Toronto, and has been working in the field of stem cells and tissue engineering for over 12 years. He is an avid tweeter (follow @DrRohinIyer) on cell therapies and regenerative medicine.
The din of the crowd calmed to a palpable whisper as Peter Zandstra, University of Toronto and Chief Scientific Officer for CCRM, took the dais: his award lecture at the Engineering Conferences International (ECI) Scale Up of Cell Therapies V meeting in San Diego, California, was about to begin.
One of the main highlights of the conference for me personally, besides the numerous talks ranging in topic from CAR-T cells to exosome manufacturing, was to see Dr. Zandstra receive the coveted ECI Scale-Up of Cell Therapies Award for outstanding achievement. This honour places him in the annals of cell therapy commercialization along with past leaders like Robert Nerem (2014) and Kim Warren (2015).
Dr. Zandstra began his lecture by talking about the hallmarks of stem cell identity (self-renewal and differentiation) and how these have remained largely unchanged through the decades. However, he explained that there is now a targeted movement in the field from cell therapies, to modified cell therapies, to in vivo modified cell therapies, to in vivo modified genes which, in turn, modify cells. “The ultimate goal of stem cell medicine,” said Dr. Zandstra, “is to grow more cells, tissues and organs on demand, and discover drugs that target stem cell function in our body.”
Touching upon how stem cell engineering can be achieved through cell engineering or “niche engineering” (the latter involving engineering of the environment surrounding the cells to drive cellular fate decisions), he opined that stem cell fate could be engineered using microreactors and bioreactors. This led to a career-long journey of discovery, development and improvement on pluripotent stem cell (PSC) cultivation, scale-up and differentiation, and high-throughput screening and high-content assays, realized through appointments as a Professor at the Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR) at the University of Toronto. This initial work also led him to question the way in which cells were conventionally grown in academic settings, and to identify and address gaps in the rational design of experiments through computational and conceptual modelling approaches including Quality by Design (QbD) as applied to bioengineering.
He discussed his evolving collaborations with other leaders in the field of stem cells and regenerative medicine, including Drs. Gordon Keller, Janet Rossant, Michael Laflamme, and Milica Radisic, which led to pre-clinical testing of PSC-derived cardiomyocytes, though challenges remain, including the inability to commercialize and industrialize these processes. “This work was not naturally suited to either an academic or an industry environment,” explained Dr. Zandstra.
The next logical step? Co-founding the Centre for Commercialization of Regenerative Medicine (now rebranded simply as “CCRM”) along with Dr. Michael May, CCRM’s President and Chief Executive Officer. Thanks to federal funding from the Centres of Excellence for Commercialization and Research (CECR) program received in 2011, CCRM, a non-profit, could begin to address gaps in cell therapy production that were amenable to process improvements at the bench scale. This included bringing a rigorous structure to technical and business aspects including reprogramming of PSCs, performing technical assessments, cost-reduction, and optimizing scale-up in bioreactors.
Dr. Zandstra then saw the need to address more challenging industrialization needs at larger scales. It was therefore logical that CCRM should upgrade its facilities and seek additional funding support, and thanks to a generous infusion of funds from GE Healthcare and the Federal Economic Development Agency (FedDev) of Southern Ontario, this led to the creation of the Centre for Advanced Therapeutic Cell Technologies (CATCT), famously inaugurated by Canada’s Prime Minister, Justin Trudeau.
The goal of this newly funded team, aptly named “BridGE,” is to bridge gaps between bench scale production and industrial scale manufacturing, while offering contract services around process development in bioreactors ranging in scale from 100mL to 100L. Personally, I’m excited by the learnings, products and processes this team will be able to deliver once we move into our newly built 40,000 sq. ft. facility in March 2017.
Dr. Zandstra explained that the CCRM vision expanded and, within five years, the non-profit has grown to five functional teams: Build (handling business development and regulatory affairs), Advance (handling cell reprogramming and technology feasibility), BridGE (explained above), Deliver (handling GMP manufacturing), and Launch (responsible for new company creation). He then touched upon the role of CCRM in spinning off two for-profit companies: ExCellThera and BlueRock Therapeutics to address manufacturing challenges associated with closed system expansion of cord blood stem cells and PSC-derived cardiomoycytes, respectively. “The challenge with expanding blood stem cells,” explained Dr. Zandstra, “is that you inevitably end up with other cells that are co-produced which negatively impact growth. So, you have to block this unwanted differentiation in a way that doesn’t damage the functional properties of cells you do want.”
The founding of BlueRock Therapeutics was supported by a USD $225 million infusion of funding from both Bayer and Versant Ventures, and CCRM played an important strategic role in supporting the great science of Drs. Keller and Laflamme at the heart of this company. It also highlights the role that Toronto is playing in the burgeoning cell therapy industry in Canada.
Dr. Zandstra spoke to his collaborations with the Ontario Institute for Regenerative Medicine (OIRM) as well as his role as executive director of Medicine by Design (MbD) at the University of Toronto, a new initiative around programmable cells (referring back to the cell engineering paradigm in contrast to the niche engineering one), and presented new data from his PhD student Shreya Shukla on progenitor T (PROT) cell generation and expansion, an area of great interest given recent momentum in the CAR-T immunotherapy field. “We may be moving from minimally manipulated cells to even synthetic cells in the future,” Dr. Zandstra envisioned.
Building on the work of Canadian pioneers James Till and Ernest McCulloch, Dr. Zandstra’s collaborative work, along with other prominent leaders in the regenerative medicine community, has helped to establish Toronto, and indeed Canada as a whole, as a nexus for stem cell industry collaboration, innovation and manufacturing. He has always pushed the boundaries in this field and been ahead of the curve in his vision of stem cells for therapeutic use and is universally respected for his intelligence, vision, and leadership. I have been lucky to have his mentorship during my own undergraduate and graduate career, and have been greatly inspired by the wisdom he has imparted during my formative years of education. It is therefore a fitting tribute that I could see him receive this well-deserved honour, and I wish him many more. We salute you Peter!