Why Manufacturing, Not Biology, May Be the Biggest Bottleneck for Personalized Cancer Vaccines

Continuing the discussion, Keith L. Knutson, PhD, Professor of Immunology, Mayo Clinic, and Eric von Hofe, PhD, CEO, CellxLife, emphasize neoantigen identification strategies and the manufacturing considerations shaping the future of personalized cancer vaccines in this third segment of an interview with BioPharm International®.

First, Dr von Hofe explains that cancer vaccine development has pursued two antigen strategies: targeting common tumor antigens expressed across many cancer types and targeting neoantigens, which are novel antigens unique to an individual's cancer, identified by comparing gene expression in tumor cells versus normal cells. One of CellxLife's vaccine platforms, for example, uses a patient's own tumor lysate—ground tumor cells containing the full array of that patient's neoantigens

"That [lysate] then can be pulsed onto dendritic cells, reintroduced to the patient, and, thereby, you're activating the immune system to all those neoantigens," Dr von Hofe says, describing how tumor lysate-based vaccines translate neoantigen discovery into clinical application.

Why will manufacturing capability determine the scalability of personalized cancer vaccines?

Next, Dr Knutson points out that vaccine development hinges on 2 fundamental questions: what to target and what part of the immune system to activate. Both questions depend heavily on manufacturing capability. He stresses that researchers must be able to identify an individual's tumor-specific proteins and manufacture them rapidly into a usable vaccine, along with manufacturing the tools needed to direct the correct immune response, such as tuned dendritic cells.

"We need to identify best practices for manufacturing,” Dr Knutson emphasizes. “We need to identify very speedy ways of manufacturing very low-cost alternatives."

Dr Knutson also notes that identifying biomarkers of tumor rejection within patient subgroups, such as certain ovarian or breast cancer populations, could enable off-the-shelf vaccine components, but adds that a personalized manufacturing component will likely remain necessary.

Get more insight in segment 1 and segment 2 of this interview.

About the speakers

Keith L. Knutson, PhD, Professor of Immunology, Mayo Clinic

Dr Knutson is a consultant in the Department of Immunology, Mayo Clinic in Florida, with a joint appointment in the Department of Cancer Biology.He serves as the director of the Mayo Clinic in Florida Cell Analysis and Cell Imaging Core.He is also co-director of the Mayo Clinic Enterprise Cancer Center’s Cancer Immunology and Immunotherapy Program and vice chair of the Mayo Clinic Enterprise Research Personnel Committee. Dr. Knutson joined the staff of Mayo Clinic in 2005 andholds the academic rank of Professor of Immunology, Mayo Clinic College of Medicine and Science. He is recognized with the distinction of the Andrew A. and Mary S. Sugg Professor of Cancer Research. He received his Bachelor of Science in Microbiology at the University of Washington and earned his PhD in Physiology and Pharmacology from the University of Georgia.

Eric von Hofe, PhD, CEO, CellxLife

Dr Hofe has more than 30 years of experience in managing and overseeing novel biotechnology approaches to cancer immunotherapy and technology development. Prior to becoming CEO of CellxLIfe, he led development efforts at AffyImmune Therapeutics raising over $20 million and advancing a novel CAR T cell therapeutic into the clinic against refractory thyroid cancer. Previously he led the development of an immunotherapeutic vaccine for breast and prostate cancer at Antigen Express, resulting in a collaboration with Merck. Prior to that he held positions at Millennium Pharmaceuticals overseeing the advancement of internal technology development projects and personalized medicine.