Semi-automated Closed System Manufacturing of Lentivirus Gene-modified Haematopoietic Stem Cells for Gene Therapy

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Oct 21

PMID 27762266

Citations 23

Authors

Jennifer E Adair

Timothy Waters

Kevin G Haworth

Sara P Kubek

Grant D Trobridge

Jonah D Hocum

Shelly Heimfeld

Hans-Peter Kiem

Affiliations

Soon will be listed here.

Abstract

Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34 blood cell products for transplantation. These cell products meet current manufacturing quality standards for both mobilized leukapheresis and bone marrow, and reconstitute human haematopoiesis in immunocompromised mice. Importantly, nonhuman primate autologous gene-modified CD34 cell products are capable of stable, polyclonal multilineage reconstitution with follow-up of more than 1 year. These data demonstrate proof of concept for point-of-care delivery of HSC gene therapy. Given the many target diseases for gene therapy, there is enormous potential for this approach to treat patients on a global scale.

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