The Translation of Cell-Based Therapies: Clinical Landscape and Manufacturing Challenges

Abstract

Cell-based therapies have the potential to make a large contribution toward currently unmet patient need and thus effective manufacture of these products is essential. Many challenges must be overcome before this can become a reality and a better definition of the manufacturing requirements for cell-based products must be obtained. The aim of this study is to inform industry and academia of current cell-based therapy clinical development and to identify gaps in their manufacturing requirements. A total of 1342 active cell-based therapy clinical trials have been identified and characterized based on cell type, target indication and trial phase. Multiple technologies have been assessed for the manufacture of these cell types in order to facilitate product translation and future process development.

Challenges of Running a GMP Facility for Regenerative Medicine in a Public Hospital

“…Generally speaking, it may be considered not convenient for pharmaceutical industry to develop ATMP in the autologous setting for severe systemic diseases. The starting biological material in this case may be affected by the underlying disease and may be of variable or poor quality [23,24], thus leading to failure in ATMP production. Moreover, the time needed to produce the autologous ATMP may be incompatible with the limited therapeutic window.…”

Enhancing cell and gene therapy manufacture through the application of advanced fluorescent optical sensors (Review)

“…While small-scale culture of cells is appropriate for in vitro studies, it is not suitable for mass production of biotechnology products for clinical use. 10 Therefore, for large scale production, highly efficient bioreactors, of up to 20 000 litres, have been developed. 11 Adherent cells, which require a surface to attach and develop, are more challenging for scale up.…”

“…This is due to the barriers presented by the removal of cells from surfaces and downstream purification and processing. 10 An interim solution, which has permitted limited scale-up of adherent cell cultures has been through the application of roller bottles and disk propagators. 9 However, a major breakthrough for adherent cell scale-up applications was the use of fibers or microcarriers as attachment surfaces.…”

“…14 Fiber and microcarrier reactors can provide very large surface areas for cells to attach and grow. 10 Microcarriers are especially promising, as surface area increases can be readily achieved through the addition of more microcarriers to the system. 15 Furthermore, porous microcarriers permit further increases in surface area.…”

Combined cell-gene therapy for lung cancer: rationale, challenges and prospects

“…MSCs have been modified and used as therapeutic vectors in several diseases [9]. In cancer, they have been successfully transduced with interferon-γ, interferon-β, thymidine kinase, or CX3CL1 expressing vectors [4] resulting in effective inhibition of tumor growth in preclinical studies.…”