High Density Cell Respirator (HDCR) for the production of vectors, viruses and vaccines

PROJECT SUMMARY/ABSTRACT
This Phase I/II STTR Fast Track proposal responds to the call from the 2018/2019 NCATS SBIR/STTR
Research Priorities to develop technologies so that “new treatments and cures for disease can be delivered to
patients more quickly”. The production of life-altering gene editing vectors, cancer killing viruses, and life-
saving vaccines currently depends on traditional cell culture techniques. A number of virus-based and cell-
based therapies have become clinical treatments for cancer, for genetically-related blindness, for
immunodeficiency, and for inborn errors of metabolism. In this exciting field, many therapies being developed
are on waitlists to be tested. However, current cell culture-based production is costly and slow to attend the
existing demand. For instance, a clinical trial for AAV-based gene editing requires 10 viral particles, a
quantity currently requiring a year for production and costing 1-2 million dollars. Thus, the cost of $400,000 to
$1,400,000 per patient for recently approved gene medicines is not surprising. These price tags simply are not
sustainable for society. In the event of a pandemic, it would take years to generate sufficient doses of vaccines
to protect the 7 billion world population by current production methods. Thus, increasing the efficiency and
speed of culture of production cell lines are common goals for manufacturing of gene editing vectors, oncolytic
viruses, and vaccines. Our joint research efforts at XDemics Corporation, the California Institute of Technology,
and the City of Hope National Medical Center, have resulted in an improved method of cell culture. Based on a
known fact that oxygen delivery is the most rate-limiting process for increasing cell density, viability, and virus
production we created a novel high density cell respirator (HDCR) (US Patent no. 10,053,660) from highly
oxygen permeable material that can be inexpensively molded into large sheets, with integrated cell retention
architecture, for efficient membrane oxygenation of adherent or suspension cells. Our hypothesis is that
elimination of shear stress and the low flow media delivery through the HDCR, enabled by the decoupling of
gas exchange via membrane oxygenation of cells, will allow for improved yield, decreased cost, and increased
speed of production of therapeutic viral vectors and viruses. We have preliminary data confirming this
hypothesis and have produced prototypes for optimization. Herein we propose Phase I studies to optimize the
design of the HDCR for cell growth and demonstrate virus production. Proposed Phase II studies will consist of
research and development of production processes for multiple viral vectors, including AAV and immuno-
oncolytic poxvirus/vaccine. We expect that the HDCR will disrupt the field of vector and virus production, by
allowing andgt;10 times greater efficiency and andgt;2-10 times greater speed of production. Our long-term goal is to
speed up production of clinically-relevant quantities of viral medicines and vaccines from years down to
months. Decreasing the cost of gene therapy vectors, cell-based immunotherapies, and vaccines will
accelerate development of novel therapies for treating cancers, gene defects, and infectious diseases.PROJECT NARRATIVE
Current technologies to produce viral based medicines and vaccines are too expensive and too inefficient to
meet the demands of the growing field of genetic medicine, and will be unable to supply the global need for
vaccines if a pandemic occurs. Our research team at XDemics Corporation, the California Institute of
Technology, and the City of Hope National Medical Center has created a new technology for growing cells and
producing genetic medicines, named high density cell respirator (HDCR), which delivers oxygen and nutrients
separately, that should make it at least 10 times more efficient and two to ten times faster at producing viruses
and gene medicines, compared to current technologies. This project proposes to finalize the design of the
HDCR for widespread use and to design the production of two promising viral based medicines using the
HDCR in order to bring this more cost-effective and time-effective production method to clinical use.