In this exclusive interview for BWB TV at Biotech Week Boston (September 2018) Shashi Murthy, PHD Professor of Chemical Engineering & Sherman Center Director at Northeastern University, explores the role played by dendritic cells in cell therapy and immunotherapy, as well as the challenges in manufacturing them.

Dr Murphy is speaking on 'Low Cost Automation to Drive Efficiency and Reproducibility' at Cell Therapy Manufacturing and Gene Therapy Congress on 5 December in Amsterdam.

Can you give us a sense of the role played by dendritic cells in cell and gene therapy and immunotherapy?

SM: Dendritic cells have come a long way in immunotherapy. Because immunotherapy relies on addressing short-circuiting of the immune system by cancer, the use of these cells is already quite widespread in discovery of biologics and characterization of biologics in immunotherapy. However, with the advent of cell-based immunotherapy, the first approved therapy was PROVENGE, and that was many years ago. However, the technology associated with cell-based immunotherapy for cancer using dendritic cells has come a long way, and I think that we're on the cusp of seeing a number of more sophisticated therapies directed in a very targeted way against different challenging indications in cancer.

But the other side to this is that there's another frontier altogether of using dendritic cells to prepare and manufacture exquisitely-targeted T-cell therapies based on neoantigens for example, and I think there, they are poised to play an equally important role. Even though they're not therapies themselves, they'll play a role in the manufacturing of those autologous therapies, and I think that's an important frontier not only for immunotherapy of cancer but also in the manufacturing realm.

What are some challenges with the manufacturing of these cells?

SM: In the vast majority of applications, dendritic cells are derived from circulating monocytes. The differentiation of monocytes into dendritic cells is a very well established process, but it has always been carried out manually in static culture. That process is extremely inefficient and low yielding, and it's also very difficult to scale. So that is by far the biggest challenge, and as the use of these cells expands not only in preclinical and basic research, but also in clinical applications, the issues associated with manufacturing become even more important.

How are you working to address these challenges?

SM: We have come a long way with respect to addressing needs in cell-based immunotherapy, but the advances have primarily been in the T-cell culture and processing realm, not so much in dendritic cells. So where we come in, my academic lab as well as the FlaskWorks company I founded, is to develop automated cell culture systems that are exquisitely designed for dendritic cell generation and dendritic cell processing, and that's how we aim to address this need.

This gets into all sorts of nitty-gritty of cell culture, like adherent versus nonadherent, adherent cells that become nonadherent for example, and our systems are geared toward addressing that. We're designing systems not only for the manufacturing of cell-based therapies based on dendritic cells, but also automated systems that can be used in preclinical research.

Shashi Murphy is speaking on 'Low Cost Automation to Drive Efficiency and Reproducibility' at Cell Therapy Manufacturing and Gene Therapy Congress on 5 December in Amsterdam. Explore the full agenda or register here.