Researchers Propose a Flexible Method for Gene Therapy Manufacture

Print 03 November 2016
Caroline Hroncich / BioPharm International

A group of researchers from the Fred Hutchinson Cancer Research Center have challenged traditional gene therapy manufacturing methods by creating a flexible closed system that if approved, could allow researchers to modify cells at an accelerated pace and in a non GMP environment. The study published on Oct. 20, 2016 in Nature Communications details the use of a semi-automated benchtop system to modify blood stem cells. The group of researchers, led by Jennifer E. Adair, PhD, research assistant professor of Medical Oncology at the University of Washington School of Medicine, demonstrated a point-of-care delivery of haematopoietic stem cell (HSC) gene therapy using animal models.

The system is a custom programmed version of Miltenyi Biotec GmbH’s CliniMACS Prodigy device that was reconfigured “to complete all of the manufacturing steps following CD34+ cell enrichment,” the study said. Additional equipment used in the process included a biosafety cabinet, sterile tubing welder, general laboratory equipment, and personal protective equipment. Adair told BioPharm International the technology’s small footprint means that it could be an effective scale-up option for gene-therapy manufacture.

“This technology condenses several large, separate pieces of equipment (for example, a centrifuge and an incubator) into a smaller footprint and eliminates the need for personnel to manually transition cell products between the large pieces of equipment,” Adair said in an email to BioPharm. “For commercial manufacturing, this technology could possibly scale-up manufacturing by maximizing available space and throughput. For non-commercial gene therapy, this technology could permit centers without cleanroom infrastructure containing this equipment to participate in gene therapy trials.”

After Adair and her team manufactured the modified cells, they compared them to cells manufactured in cleanrooms. Researchers noted the stem cells were of similar quality to those manufactured via traditional methods. To determine efficacy and safety, the team transplanted the cells into two myloablated monkeys and the cells were successfully proliferated the animal’s blood streams. The study notes that the monkeys demonstrated no adverse events related to manufacturing methods. Adair said that if this technology is approved, it could have the potential to treat any disease for which gene therapy is a potential treatment including “inherited immune deficiencies, hemoglobinopathies, sickle cell disease, HIV, cancer, leukodystrophies, and inherited bone marrow failure disorders.”

The semi-automated device reduces the space and staff needed to modify cells and if approved, would cost approximately $150,000 to purchase, an article from the Fred Hutchinson Cancer Research Center noted. The researchers spent 18-months developing the technology and they said it could have the potential to bring targeted therapies to emerging markets. Facilities with the equipment for gene therapy manufacture are currently only in seven countries including the US, Spain, France, United Kingdom, Italy, Germany, and Australia, the researchers noted. Therefore, if gene-therapy is approved, distribution may be a barrier to access for patients in emerging markets.

This technology is still in the early stages of development, and there are currently no approved uses for gene therapy, but Adair is hopeful that one day it will have the potential to treat patients all over the world. She said, “This technology significantly reduces space and equipment requirements, and we are working toward making this technology user-friendly for medically trained staff. My hope is that this technology could be available to developing countries in the future, opening the door to treating millions of patients with gene therapy."

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