“cGMP gene therapy in a box” is one step closer, says new manuscript

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Automated stem cell and gene therapy was once a pipe dream that has lately been inching closer to reality, owing to new and ongoing initiatives aimed at development new manufacturing solutions to facilitate its implementation.

One such initiative is the European Union’s recently launched AUTOSTEM program.

One of the main hurdles in the development of manufacturing processes for cell and gene therapies is the  availability of suitable manufacturing equipment. Because of the inherent complexity of the cascade of operations necessary to develop a functional gene-modified cell-based therapy product (which are related to the ex vivo manipulation of cells and includes isolation, genetic modification and expansion), equipment that can provide closed system automation, while desired, is not readily available. These steps include

A research group, led by Dr. Hans-Peter Kiem at the University of Washington and the Fred Hutchinson Cancer Research Center described, in a manuscript published in Nature Communications, the modification of a commercial cell processing instrument into a semi-closed unit for the manufacturing of hematopoietic stem cell-based gene therapies.

Titled Semi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy, the manuscript describes the use of Miltenyi Biotec’s CliniMACS platform alongside custom programmed modules to develop a “semi-closed”system which allows for the isolation and modification of CD34+ cells suitable for human infusion and haematopoietic repopulation.

Cells, which came from both BM and HPC-A sources, were transduced and enriched with minimal user input by reconfiguring the CliniMACS programs via multiple separate functions to define the individual process steps (separation, culture, fluid addition, spinoculation, sampling, harvest and formulation). All of these steps were done in a research lab (and not cGMP) – despite that, the authors showed that the process meets cGMP guidelines for safety. Transduction was achieved by using an anti-HIV LV vector, while cells were cultured the same growth factors and media used in human cell product manufacture.

As expected, the viability of the final resulting cell product following transduction, as measured by trypan blue dye exclusion, went from 86% at initial culture to 40%.

The authors argue that, because of the efficiency of the system, alongside its portable and self-contained nature,  together with the fact that it was shown to meet cGMP guidelines without it being used in a cGMP lab, can eliminate the need for local cGMP facility infrastructure and reduce the need for trained staff. This can, they further claim, translate into significant cost advantages as the system is suitable for direct point-of-care implementation.

The entire manuscript can be read here.




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