Next-generation separation technologies for the advanced manufacturing of oncolytic viruses

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Oncolytic viruses (OVs) are a special class of bio-therapeutic molecules being developed for the treatment of cancer. Given the recent approval of the first OV product (for advanced melanoma) by the US FDA, the excitement and expectations are at an all time high.  Currently over 40 clinical trials are being conducted worldwide and bio-therapeutic companies are making major investments in expanding and accelerating their pipeline of OV products. Canada is a major player in the OV field given our national network of world-class researchers (BioCanRx), who are discovering new OVs and novel ways to deliver OVs into cancer cells, and growing industry sector.  The commercial success of OV-based therapies is critically dependent on the development of large-scale OV manufacturing process that can achieve the activity and purity requirements established by regulatory agencies (e.g. Health Canada, FDA) while also being cost-effective. Given recent advances in 'upstream' OV manufacturing capacity, the accompanying 'downstream' separation processes are the major 'bottleneck' in OV manufacturing. The long-term vision of my research program is build the know-how, train the HQP, and develop the technologies to fix this problem.  In the short term, 4 PhD and 13 undergraduate students will carry out three interconnected projects to develop separation technologies that solve the critical 'technology gaps' that currently exist in large-scale OV manufacturing - they include: 1) Rational design of membrane chromatography processes for the production of OVs 2) Simultaneous purification, stabilization, and sterilization of OVs via diafiltration membrane process 3) Aptamer affinity chromatography process for the single-step purification of OVs The technologies will be developed for different OV candidates, however a significant focus will be on Maraba rhabdovirus given its potential use in the treatment of non-small cell lung cancer, the leading cause of cancer-related deaths in North America. Because bio-therapeutic manufacturers are reluctant to adopt new separation processes without extensive experimental validation, each project will include an assessment of process reproducibility and the development of theoretical frameworks. McMaster is the ideal venue to conduct this research given its world-class user facilities (Biointerfaces Institute, Centre for Microbial Chemical Biology) with state-of-the-art equipment. Most importantly, McMaster is also home to the Fitzhenry Manufacturing Facility (FMF), one of only two GMP suites in Canada with experience in producing pharmaceutical-grade OV products. While the FMF does not have the capacity to be used for commercial-scale production, it will allow for my team to demonstrate the 'proof-of-concept' at pilot-scale manufacturing. To my knowledge, there is no other group in Canada that has our expertise in separation processes plus this combination of infrastructure and equipment to execute a study of this kind.